<?xml version="1.0"?>
<feed xmlns="http://www.w3.org/2005/Atom" xml:lang="en-GB">
	<id>https://embryology.med.unsw.edu.au/embryology/api.php?action=feedcontributions&amp;feedformat=atom&amp;user=Z3417796</id>
	<title>Embryology - User contributions [en-gb]</title>
	<link rel="self" type="application/atom+xml" href="https://embryology.med.unsw.edu.au/embryology/api.php?action=feedcontributions&amp;feedformat=atom&amp;user=Z3417796"/>
	<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Special:Contributions/Z3417796"/>
	<updated>2026-10-01T15:16:15Z</updated>
	<subtitle>User contributions</subtitle>
	<generator>MediaWiki 1.39.10</generator>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162041</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162041"/>
		<updated>2014-11-02T15:10:46Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 11===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
===Lab 12===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:09, 29 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;br /&gt;
&lt;br /&gt;
===Lab 11===&lt;br /&gt;
'''Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells.''': &lt;br /&gt;
In this investigation an innovative, stepwise chemical procedure for the differentiating of human embryonic stem cells (hESC’s) and induced pluripotent stem (IPS) cells into effective retinal ganglion cells (RGS’s) was examined in the context of a potential advancements to the development of RGC replacement therapy. To proficiently induce the differentiation of the acquired stem cells into ganglion cells, a cell culture with a single culture chemical, DAPT- notch inhibitor was utilised. The hESC’s and IPS cells were differentiated into neuroprogenitors known as neural rosettes demonstrating that notch signalling serves a vital function in stem cell differentiation- and potentially a target for future clinical application. The expression of specific neural and RCG biomarkers (BRN3A, BRN3B, ATOH7/Math5, γ-synuclein, Islet-1, and THY-1) were then inspected. The resulting data demonstrates that roughly 30% of the differentiating stem cells were positive for the expression of RGC markers in addition to the neuronal biomarker TUJI. The differentiated RGC’s were able to generate action potentials as well as create impulsive excitatory postsynaptic currents, which signify that mature, functioning RGC’s were produced. This data effectively demonstrates that the culturing of PAX6/RX-positive stem cells within a single chemical (DAPT) can stimulate these cells to undergo differentiation into mature, functional RGCs.&lt;br /&gt;
&amp;lt;ref name= '''PMID24493857'''&amp;gt;&amp;lt;pubmed&amp;gt;24493857&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162038</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162038"/>
		<updated>2014-11-02T15:05:57Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 11===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
===Lab 12===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:09, 29 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;br /&gt;
&lt;br /&gt;
===Lab 11===&lt;br /&gt;
'''Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells.''': &lt;br /&gt;
In this investigation an innovative, stepwise chemical procedure for the differentiating of human embryonic stem cells (hESC’s) and induced pluripotent stem (IPS) cells into effective retinal ganglion cells (RGS’s) was examined in the context of a potential advancements to the development of RGC replacement therapy. To proficiently induce the differentiation of the acquired stem cells into ganglion cells, a cell culture with a single culture chemical, DAPT- notch inhibitor. The hESC’s and IPS cells were differentiated into neuroprogenitors known as neural rosettes demonstrating that notch signalling serves a vital function in stem cell differentiation- and potentially a target for clinical future application. The expression of specific neural and RCG biomarkers (BRN3A, BRN3B, ATOH7/Math5, γ-synuclein, Islet-1, and THY-1) were then inspected. The resulting data demonstrates that roughly 30% of the differentiating stem cells were positive for the expression of RGC markers in addition to the neuronal biomarker TUJI. The differentiated RGC’s were able to generate action potentials as well as impulsive excitatory postsynaptic currents, which signify that mature, functioning RGC’s were produced. This data effectively demonstrates that the culturing of PAX6/RX-positive stem cells within a single chemical (DAPT) can stimulate these cells to undergo differentiation into mature, functional RGCs.&lt;br /&gt;
&amp;lt;ref name= '''PMID24493857'''&amp;gt;&amp;lt;pubmed&amp;gt;24493857&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162035</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=162035"/>
		<updated>2014-11-02T14:31:02Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 11===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
===Lab 12===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:09, 29 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;br /&gt;
&lt;br /&gt;
===Lab 11===&lt;br /&gt;
'''Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells.''': &lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= '''PMID24493857'''&amp;gt;&amp;lt;pubmed&amp;gt;24493857&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=161300</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=161300"/>
		<updated>2014-10-29T01:10:00Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 11===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
===Lab 12===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:09, 29 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157268</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157268"/>
		<updated>2014-10-23T11:15:52Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: /* Glands */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, the periderm and and basal layer of the developing skin was observed. The basal cell keratins K5 and K14 were also observed from 8 weeks onwards&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed; with the stratum intermedium forming between the basal and periderm layers .  Kertain filaments, such as K8 and K19 have been encircled- they feature during fetal skin development but are absent in the adult epidermis. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 is not observed) &amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. || image&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. The fetal extra-cellular matrix also differs from that of the adult- mainly in terms of the collagen type&amp;lt;ref name= PMID8292556&amp;gt;&amp;lt;pubmed&amp;gt;8292556&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   and amount of glycosaminoglycans present&amp;lt;ref name= PMID2027330&amp;gt;&amp;lt;pubmed&amp;gt;2027330&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis are released- signaling for the induction hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage !! Description &lt;br /&gt;
|-&lt;br /&gt;
| Undifferentiated Epithelium || Through reciprocal interactions and ‘first dermal signaling’, cells from the stratum basale grow into the underlying dermis. The signaling pathway, however, has not been fully identified&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Placode || The ‘first dermal signals’ influence epithelial cells to develop a placode- a thickening of the columnar cells.  It is theorised that varying intrinsic dermal signals lead to the expression of various placodes and consequently, the differences in the expression of hair thickness/size throughout the body&amp;lt;ref name= PMID10529418&amp;gt;&amp;lt;pubmed&amp;gt;10529418&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. The specific combination of promoter and repressor activators for hair development, is also theorised to characterise for the regional differences in eventual hair expression&amp;lt;ref name= PMID10431226&amp;gt;&amp;lt;pubmed&amp;gt;10431226&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Germ || WNT Signalling is believed to have a role in the induction of the dermal condesate&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Platelet-derived growth factor-A molecules from the placode, also contributes to the induction of the dermal condensate. The development of the dermal condensate helps further induce the downward growth of the placode. &lt;br /&gt;
Through secreted proteins such as Sonic Hedgehog, the placode continues to proliferate and enclose the dermal condensate. This eventually forms a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings.&lt;br /&gt;
|-&lt;br /&gt;
| Peg || Sonic Hedgehog and the induction of a ‘secondary dermal signal’  (characterisation unknown) leads to a significant down-growth and proliferation of the follilular epithelium&amp;lt;ref name= PMID9768360&amp;gt;&amp;lt;pubmed&amp;gt;9768360&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
In this stage, it is also believed that the polarity of the hair follicle (the angle at which hair-follicles grow in relation to skin) and the architecture of the hair follicle itself (straight hair, wavy hair, etc) is regulated in part by Sonic Hedgehog and TGF-a signaling respectively&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|-&lt;br /&gt;
| Bulbous Peg || This stage is characterised by the appearance of the hair follicle bulb. Further and significant differentiation of the inner root sheeth and the hair shaft also characterises this stage&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The epithelial cells within the hair bulb, begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
Proteins such as Notch1 are believed to help regulate the phenotype of keratinocytes as they differentiate&amp;lt;ref name= PMID10804183&amp;gt;&amp;lt;pubmed&amp;gt;10804183&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:---|frame|right|middle|180x150px|Undifferentiated Epithelium|]]||[[Image:Fetal Hair Follicle Development - Week 8-12.JPG|frame|right|middle|180x150px|Week 8-12|]]||[[Image:Fetal Hair Follicle Development - Week 12-14.JPG|frame|right|middle|180x150px|Week 12-14|]]|| [[Image:Fetal Hair Follicle Development - Week 13-16.JPG|frame|right|middle|180x150px|Week 13-16|]] || [[Image:Fetal Hair Follicle Development - Week 19-21.JPG|frame|right|middle|180x150px|Week 19-21|]]|| [[Image:Fetal Hair Follicle Development - Week 23-28 .JPG|frame|right|middle|180x150px|Week 23-28|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:30%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Feta Nail Development - Week 9-10.jpg|frame|right|middle|135x115px|Week 9-10|]]|| [[Image:Fetal Nail Development - Week 11-12.jpg|frame|right|middle|135x115px|Week 11-12 |]] || [[Image:Fetal Nail Development - Week 13-14 .jpg|frame|right|middle|135x115px|Week 13-14|]]|| [[Image:Mature Nail .jpg|frame|right|middle|135x115px|Mature Nail|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description !! Image&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands || *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|| [[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  || Image&lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || &lt;br /&gt;
There are two major kinds of sweat glands present in humans, both of which develop from downgrowths of the epidermis into the underlying dermis. Sweat glands have been histologically identified in studies from week 21 of development.&lt;br /&gt;
&lt;br /&gt;
Eccrine Sweat Glands&lt;br /&gt;
* Located in the skin with distributions throughout most of the body &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Function in thermoregulation and excretion of excess electrolytes and water &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevier Limited. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function initiating shortly after birth &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
Apocrine Sweat Glands&lt;br /&gt;
*Located in the skin of the axilla, pubic and perianal areas and nipple areolae &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* May function in a form of olfactory communication &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevier Limited. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function originating at puberty &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
 &lt;br /&gt;
|| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]] &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Video===&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
* '''1900''' - Bardeen used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study of nail development, anatomy and physiology. Thus, as such technology advances scientists have been able to uncover the morphological details of the nail and understand the changes that occur during nail development. A review of the history allows us to recognize the major contributor to this field. History of research on nail development also reveals the interesting debate on the origins of keratinized cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* German scientists Unna and Pinkus were both highly reputable dermatologists who conducted a great deal of research on the development of the skin and associated structures. They were   (&amp;lt;ref name= PMID12581143&amp;gt;&amp;lt;pubmed&amp;gt;12581143&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &amp;lt;ref&amp;gt;Roberts, H. L., &amp;amp; Walker, N. (1929). PAUL GERSON UNNA. British Journal of Dermatology, 41(4), 157-160.&amp;lt;/ref&amp;gt;)&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease. &lt;br /&gt;
* Based on their findings both scientists proposed that the nail matrix structure gives rise to the entire nail plate during normal fetal development. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|170x145px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the fetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a &amp;quot;tri-partite&amp;quot; origin of the nail plate from three tissue origins (1) the proximal nail fold (2) the matrix and (3) bed. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
* Prior to the 1900’s it was difficulty in obtaining normal fetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might allows us to infer the mechanism of nail plate genesis. Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate. &amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157250</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157250"/>
		<updated>2014-10-23T11:12:23Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: /* Glands */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, the periderm and and basal layer of the developing skin was observed. The basal cell keratins K5 and K14 were also observed from 8 weeks onwards&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed; with the stratum intermedium forming between the basal and periderm layers .  Kertain filaments, such as K8 and K19 have been encircled- they feature during fetal skin development but are absent in the adult epidermis. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 is not observed) &amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. || image&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. The fetal extra-cellular matrix also differs from that of the adult- mainly in terms of the collagen type&amp;lt;ref name= PMID8292556&amp;gt;&amp;lt;pubmed&amp;gt;8292556&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   and amount of glycosaminoglycans present&amp;lt;ref name= PMID2027330&amp;gt;&amp;lt;pubmed&amp;gt;2027330&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis are released- signaling for the induction hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage !! Description &lt;br /&gt;
|-&lt;br /&gt;
| Undifferentiated Epithelium || Through reciprocal interactions and ‘first dermal signaling’, cells from the stratum basale grow into the underlying dermis. The signaling pathway, however, has not been fully identified&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Placode || The ‘first dermal signals’ influence epithelial cells to develop a placode- a thickening of the columnar cells.  It is theorised that varying intrinsic dermal signals lead to the expression of various placodes and consequently, the differences in the expression of hair thickness/size throughout the body&amp;lt;ref name= PMID10529418&amp;gt;&amp;lt;pubmed&amp;gt;10529418&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. The specific combination of promoter and repressor activators for hair development, is also theorised to characterise for the regional differences in eventual hair expression&amp;lt;ref name= PMID10431226&amp;gt;&amp;lt;pubmed&amp;gt;10431226&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Germ || WNT Signalling is believed to have a role in the induction of the dermal condesate&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Platelet-derived growth factor-A molecules from the placode, also contributes to the induction of the dermal condensate. The development of the dermal condensate helps further induce the downward growth of the placode. &lt;br /&gt;
Through secreted proteins such as Sonic Hedgehog, the placode continues to proliferate and enclose the dermal condensate. This eventually forms a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings.&lt;br /&gt;
|-&lt;br /&gt;
| Peg || Sonic Hedgehog and the induction of a ‘secondary dermal signal’  (characterisation unknown) leads to a significant down-growth and proliferation of the follilular epithelium&amp;lt;ref name= PMID9768360&amp;gt;&amp;lt;pubmed&amp;gt;9768360&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
In this stage, it is also believed that the polarity of the hair follicle (the angle at which hair-follicles grow in relation to skin) and the architecture of the hair follicle itself (straight hair, wavy hair, etc) is regulated in part by Sonic Hedgehog and TGF-a signaling respectively&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|-&lt;br /&gt;
| Bulbous Peg || This stage is characterised by the appearance of the hair follicle bulb. Further and significant differentiation of the inner root sheeth and the hair shaft also characterises this stage&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The epithelial cells within the hair bulb, begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
Proteins such as Notch1 are believed to help regulate the phenotype of keratinocytes as they differentiate&amp;lt;ref name= PMID10804183&amp;gt;&amp;lt;pubmed&amp;gt;10804183&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:---|frame|right|middle|180x150px|Undifferentiated Epithelium|]]||[[Image:Fetal Hair Follicle Development - Week 8-12.JPG|frame|right|middle|180x150px|Week 8-12|]]||[[Image:Fetal Hair Follicle Development - Week 12-14.JPG|frame|right|middle|180x150px|Week 12-14|]]|| [[Image:Fetal Hair Follicle Development - Week 13-16.JPG|frame|right|middle|180x150px|Week 13-16|]] || [[Image:Fetal Hair Follicle Development - Week 19-21.JPG|frame|right|middle|180x150px|Week 19-21|]]|| [[Image:Fetal Hair Follicle Development - Week 23-28 .JPG|frame|right|middle|180x150px|Week 23-28|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:30%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Feta Nail Development - Week 9-10.jpg|frame|right|middle|135x115px|Week 9-10|]]|| [[Image:Fetal Nail Development - Week 11-12.jpg|frame|right|middle|135x115px|Week 11-12 |]] || [[Image:Fetal Nail Development - Week 13-14 .jpg|frame|right|middle|135x115px|Week 13-14|]]|| [[Image:Mature Nail .jpg|frame|right|middle|135x115px|Mature Nail|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description !! Image&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands || *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|| [[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  || Image&lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || &lt;br /&gt;
There are two major kinds of sweat glands present in humans, both of develop from downgrowths of epidermis into the underlying dermis. Sweat glands have been histologically identified in studies from week 21 of development.&lt;br /&gt;
&lt;br /&gt;
Eccrine Sweat Glands&lt;br /&gt;
* Located in the skin with distributions throughout most of the body &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Function in thermoregulation and excretion of excess electrolytes and water &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevier Limited. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function initiating shortly after birth &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
Apocrine Sweat Glands&lt;br /&gt;
*Located in the skin of the axilla, pubic and perianal areas and nipple areolae &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* May function in a form of olfactory communication &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevier Limited. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function originating at puberty &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
 &lt;br /&gt;
|| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]] &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Video===&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
* '''1900''' - Bardeen used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study of nail development, anatomy and physiology. Thus, as such technology advances scientists have been able to uncover the morphological details of the nail and understand the changes that occur during nail development. A review of the history allows us to recognize the major contributor to this field. History of research on nail development also reveals the interesting debate on the origins of keratinized cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* German scientists Unna and Pinkus were both highly reputable dermatologists who conducted a great deal of research on the development of the skin and associated structures. They were   (&amp;lt;ref name= PMID12581143&amp;gt;&amp;lt;pubmed&amp;gt;12581143&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &amp;lt;ref&amp;gt;Roberts, H. L., &amp;amp; Walker, N. (1929). PAUL GERSON UNNA. British Journal of Dermatology, 41(4), 157-160.&amp;lt;/ref&amp;gt;)&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease. &lt;br /&gt;
* Based on their findings both scientists proposed that the nail matrix structure gives rise to the entire nail plate during normal fetal development. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|170x145px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the fetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a &amp;quot;tri-partite&amp;quot; origin of the nail plate from three tissue origins (1) the proximal nail fold (2) the matrix and (3) bed. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
* Prior to the 1900’s it was difficulty in obtaining normal fetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might allows us to infer the mechanism of nail plate genesis. Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate. &amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157244</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157244"/>
		<updated>2014-10-23T11:05:53Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: /* Glands */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, the periderm and and basal layer of the developing skin was observed. The basal cell keratins K5 and K14 were also observed from 8 weeks onwards&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed; with the stratum intermedium forming between the basal and periderm layers .  Kertain filaments, such as K8 and K19 have been encircled- they feature during fetal skin development but are absent in the adult epidermis. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 is not observed) &amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. || image&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. The fetal extra-cellular matrix also differs from that of the adult- mainly in terms of the collagen type&amp;lt;ref name= PMID8292556&amp;gt;&amp;lt;pubmed&amp;gt;8292556&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   and amount of glycosaminoglycans present&amp;lt;ref name= PMID2027330&amp;gt;&amp;lt;pubmed&amp;gt;2027330&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis are released- signaling for the induction hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage !! Description &lt;br /&gt;
|-&lt;br /&gt;
| Undifferentiated Epithelium || Through reciprocal interactions and ‘first dermal signaling’, cells from the stratum basale grow into the underlying dermis. The signaling pathway, however, has not been fully identified&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Placode || The ‘first dermal signals’ influence epithelial cells to develop a placode- a thickening of the columnar cells.  It is theorised that varying intrinsic dermal signals lead to the expression of various placodes and consequently, the differences in the expression of hair thickness/size throughout the body&amp;lt;ref name= PMID10529418&amp;gt;&amp;lt;pubmed&amp;gt;10529418&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. The specific combination of promoter and repressor activators for hair development, is also theorised to characterise for the regional differences in eventual hair expression&amp;lt;ref name= PMID10431226&amp;gt;&amp;lt;pubmed&amp;gt;10431226&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Germ || WNT Signalling is believed to have a role in the induction of the dermal condesate&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Platelet-derived growth factor-A molecules from the placode, also contributes to the induction of the dermal condensate. The development of the dermal condensate helps further induce the downward growth of the placode. &lt;br /&gt;
Through secreted proteins such as Sonic Hedgehog, the placode continues to proliferate and enclose the dermal condensate. This eventually forms a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings.&lt;br /&gt;
|-&lt;br /&gt;
| Peg || Sonic Hedgehog and the induction of a ‘secondary dermal signal’  (characterisation unknown) leads to a significant down-growth and proliferation of the follilular epithelium&amp;lt;ref name= PMID9768360&amp;gt;&amp;lt;pubmed&amp;gt;9768360&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
In this stage, it is also believed that the polarity of the hair follicle (the angle at which hair-follicles grow in relation to skin) and the architecture of the hair follicle itself (straight hair, wavy hair, etc) is regulated in part by Sonic Hedgehog and TGF-a signaling respectively&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|-&lt;br /&gt;
| Bulbous Peg || This stage is characterised by the appearance of the hair follicle bulb. Further and significant differentiation of the inner root sheeth and the hair shaft also characterises this stage&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The epithelial cells within the hair bulb, begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
Proteins such as Notch1 are believed to help regulate the phenotype of keratinocytes as they differentiate&amp;lt;ref name= PMID10804183&amp;gt;&amp;lt;pubmed&amp;gt;10804183&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:---|frame|right|middle|180x150px|Undifferentiated Epithelium|]]||[[Image:Fetal Hair Follicle Development - Week 8-12.JPG|frame|right|middle|180x150px|Week 8-12|]]||[[Image:Fetal Hair Follicle Development - Week 12-14.JPG|frame|right|middle|180x150px|Week 12-14|]]|| [[Image:Fetal Hair Follicle Development - Week 13-16.JPG|frame|right|middle|180x150px|Week 13-16|]] || [[Image:Fetal Hair Follicle Development - Week 19-21.JPG|frame|right|middle|180x150px|Week 19-21|]]|| [[Image:Fetal Hair Follicle Development - Week 23-28 .JPG|frame|right|middle|180x150px|Week 23-28|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:30%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Feta Nail Development - Week 9-10.jpg|frame|right|middle|135x115px|Week 9-10|]]|| [[Image:Fetal Nail Development - Week 11-12.jpg|frame|right|middle|135x115px|Week 11-12 |]] || [[Image:Fetal Nail Development - Week 13-14 .jpg|frame|right|middle|135x115px|Week 13-14|]]|| [[Image:Mature Nail .jpg|frame|right|middle|135x115px|Mature Nail|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description !! Image&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands || *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|| [[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  || Image&lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || &lt;br /&gt;
There are two major kinds of sweat glands present in humans, both of develop from downgrowths of epidermis into the underlying dermis. Sweat glands have been histologically identified in studies from week 21 of development.&lt;br /&gt;
&lt;br /&gt;
Eccrine Sweat Glands&lt;br /&gt;
* Located in the skin with distributions throughout most of the body &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Function in thermoregulation and excretion of excess electrolytes and water &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevie. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function initiating shortly after birth &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
Apocrine Sweat Glands&lt;br /&gt;
*Located in the skin of the axilla, pubic and perianal areas and nipple areolae &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* May function in a form of olfactory communication &amp;lt;ref&amp;gt;Bolognia, J.L., Jorizzo, J.L. &amp;amp; Schaffer J.V. (2012). Dermatology (3rd ed.). Elsevie. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Present at birth with function originating at puberty &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
 &lt;br /&gt;
|| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]] &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Video===&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
* '''1900''' - Bardeen used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study of nail development, anatomy and physiology. Thus, as such technology advances scientists have been able to uncover the morphological details of the nail and understand the changes that occur during nail development. A review of the history allows us to recognize the major contributor to this field. History of research on nail development also reveals the interesting debate on the origins of keratinized cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* German scientists Unna and Pinkus were both highly reputable dermatologists who conducted a great deal of research on the development of the skin and associated structures. They were   (&amp;lt;ref name= PMID12581143&amp;gt;&amp;lt;pubmed&amp;gt;12581143&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &amp;lt;ref&amp;gt;Roberts, H. L., &amp;amp; Walker, N. (1929). PAUL GERSON UNNA. British Journal of Dermatology, 41(4), 157-160.&amp;lt;/ref&amp;gt;)&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease. &lt;br /&gt;
* Based on their findings both scientists proposed that the nail matrix structure gives rise to the entire nail plate during normal fetal development. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|170x145px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the fetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a &amp;quot;tri-partite&amp;quot; origin of the nail plate from three tissue origins (1) the proximal nail fold (2) the matrix and (3) bed. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
* Prior to the 1900’s it was difficulty in obtaining normal fetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might allows us to infer the mechanism of nail plate genesis. Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate. &amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157220</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157220"/>
		<updated>2014-10-23T10:54:37Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, the periderm and and basal layer of the developing skin was observed. The basal cell keratins K5 and K14 were also observed from 8 weeks onwards&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed; with the stratum intermedium forming between the basal and periderm layers .  Kertain filaments, such as K8 and K19 have been encircled- they feature during fetal skin development but are absent in the adult epidermis. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 is not observed) &amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. || image&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. The fetal extra-cellular matrix also differs from that of the adult- mainly in terms of the collagen type&amp;lt;ref name= PMID8292556&amp;gt;&amp;lt;pubmed&amp;gt;8292556&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   and amount of glycosaminoglycans present&amp;lt;ref name= PMID2027330&amp;gt;&amp;lt;pubmed&amp;gt;2027330&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis are released- signaling for the induction hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage !! Description &lt;br /&gt;
|-&lt;br /&gt;
| Undifferentiated Epithelium || Through reciprocal interactions and ‘first dermal signaling’, cells from the stratum basale grow into the underlying dermis. The signaling pathway, however, has not been fully identified&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Placode || The ‘first dermal signals’ influence epithelial cells to develop a placode- a thickening of the columnar cells.  It is theorised that varying intrinsic dermal signals lead to the expression of various placodes and consequently, the differences in the expression of hair thickness/size throughout the body&amp;lt;ref name= PMID10529418&amp;gt;&amp;lt;pubmed&amp;gt;10529418&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. The specific combination of promoter and repressor activators for hair development, is also theorised to characterise for the regional differences in eventual hair expression&amp;lt;ref name= PMID10431226&amp;gt;&amp;lt;pubmed&amp;gt;10431226&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Germ || WNT Signalling is believed to have a role in the induction of the dermal condesate&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Platelet-derived growth factor-A molecules from the placode, also contributes to the induction of the dermal condensate. The development of the dermal condensate helps further induce the downward growth of the placode. &lt;br /&gt;
Through secreted proteins such as Sonic Hedgehog, the placode continues to proliferate and enclose the dermal condensate. This eventually forms a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings.&lt;br /&gt;
|-&lt;br /&gt;
| Peg || Sonic Hedgehog and the induction of a ‘secondary dermal signal’  (characterisation unknown) leads to a significant down-growth and proliferation of the follilular epithelium&amp;lt;ref name= PMID9768360&amp;gt;&amp;lt;pubmed&amp;gt;9768360&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
In this stage, it is also believed that the polarity of the hair follicle (the angle at which hair-follicles grow in relation to skin) and the architecture of the hair follicle itself (straight hair, wavy hair, etc) is regulated in part by Sonic Hedgehog and TGF-a signaling respectively&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|-&lt;br /&gt;
| Bulbous Peg || This stage is characterised by the appearance of the hair follicle bulb. Further and significant differentiation of the inner root sheeth and the hair shaft also characterises this stage&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The epithelial cells within the hair bulb, begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
Proteins such as Notch1 are believed to help regulate the phenotype of keratinocytes as they differentiate&amp;lt;ref name= PMID10804183&amp;gt;&amp;lt;pubmed&amp;gt;10804183&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:---|frame|right|middle|180x150px|Undifferentiated Epithelium|]]||[[Image:Fetal Hair Follicle Development - Week 8-12.JPG|frame|right|middle|180x150px|Week 8-12|]]||[[Image:Fetal Hair Follicle Development - Week 12-14.JPG|frame|right|middle|180x150px|Week 12-14|]]|| [[Image:Fetal Hair Follicle Development - Week 13-16.JPG|frame|right|middle|180x150px|Week 13-16|]] || [[Image:Fetal Hair Follicle Development - Week 19-21.JPG|frame|right|middle|180x150px|Week 19-21|]]|| [[Image:Fetal Hair Follicle Development - Week 23-28 .JPG|frame|right|middle|180x150px|Week 23-28|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:30%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Feta Nail Development - Week 9-10.jpg|frame|right|middle|135x115px|Week 9-10|]]|| [[Image:Fetal Nail Development - Week 11-12.jpg|frame|right|middle|135x115px|Week 11-12 |]] || [[Image:Fetal Nail Development - Week 13-14 .jpg|frame|right|middle|135x115px|Week 13-14|]]|| [[Image:Mature Nail .jpg|frame|right|middle|135x115px|Mature Nail|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description !! Image&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands || *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|| [[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  || Image&lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || &lt;br /&gt;
There are two major kinds of sweat glands present in humans, both of develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21.&lt;br /&gt;
&lt;br /&gt;
Eccrine Sweat Glands&lt;br /&gt;
* Located in the skin with distributions throughout most of the body &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* Function in thermoregulation and excretion of excess electrolytes and water *&lt;br /&gt;
* Present at birth with function initiating shorting after birth &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
Apocrine Sweat Glands&lt;br /&gt;
*Located in the skin of the axilla, pubic and perianal areas and nipple areolae &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* May function in a form of olfactory communication *&lt;br /&gt;
* Present at birth with function originating at puberty &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
 &lt;br /&gt;
|| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]] &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Video===&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
* '''1900''' - Bardeen used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study of nail development, anatomy and physiology. Thus, as such technology advances scientists have been able to uncover the morphological details of the nail and understand the changes that occur during nail development. A review of the history allows us to recognize the major contributor to this field. History of research on nail development also reveals the interesting debate on the origins of keratinized cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* German scientists Unna and Pinkus were both highly reputable dermatologists who conducted a great deal of research on the development of the skin and associated structures. They were   (&amp;lt;ref name= PMID12581143&amp;gt;&amp;lt;pubmed&amp;gt;12581143&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &amp;lt;ref&amp;gt;Roberts, H. L., &amp;amp; Walker, N. (1929). PAUL GERSON UNNA. British Journal of Dermatology, 41(4), 157-160.&amp;lt;/ref&amp;gt;)&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease. &lt;br /&gt;
* Based on their findings both scientists proposed that the nail matrix structure gives rise to the entire nail plate during normal fetal development. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|170x145px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the fetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a &amp;quot;tri-partite&amp;quot; origin of the nail plate from three tissue origins (1) the proximal nail fold (2) the matrix and (3) bed. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
* Prior to the 1900’s it was difficulty in obtaining normal fetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might allows us to infer the mechanism of nail plate genesis. Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate. &amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157193</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=157193"/>
		<updated>2014-10-23T10:38:30Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: /* Glands */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, the periderm and and basal layer of the developing skin was observed. The basal cell keratins K5 and K14 were also observed from 8 weeks onwards&amp;lt;ref name= PMID2413039&amp;gt;&amp;lt;pubmed&amp;gt;2413039&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed; with the stratum intermedium forming between the basal and periderm layers .  Kertain filaments, such as K8 and K19 have been encircled- they feature during fetal skin development but are absent in the adult epidermis. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 is not observed) &amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. || image&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development&amp;lt;ref name= PMID19701759&amp;gt;&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. The fetal extra-cellular matrix also differs from that of the adult- mainly in terms of the collagen type&amp;lt;ref name= PMID8292556&amp;gt;&amp;lt;pubmed&amp;gt;8292556&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   and amount of glycosaminoglycans present&amp;lt;ref name= PMID2027330&amp;gt;&amp;lt;pubmed&amp;gt;2027330&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.   || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis are released- signaling for the induction hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage !! Description &lt;br /&gt;
|-&lt;br /&gt;
| Undifferentiated Epithelium || Through reciprocal interactions and ‘first dermal signaling’, cells from the stratum basale grow into the underlying dermis. The signaling pathway, however, has not been fully identified&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Placode || The ‘first dermal signals’ influence epithelial cells to develop a placode- a thickening of the columnar cells.  It is theorised that varying intrinsic dermal signals lead to the expression of various placodes and consequently, the differences in the expression of hair thickness/size throughout the body&amp;lt;ref name= PMID10529418&amp;gt;&amp;lt;pubmed&amp;gt;10529418&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. The specific combination of promoter and repressor activators for hair development, is also theorised to characterise for the regional differences in eventual hair expression&amp;lt;ref name= PMID10431226&amp;gt;&amp;lt;pubmed&amp;gt;10431226&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Germ || WNT Signalling is believed to have a role in the induction of the dermal condesate&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Platelet-derived growth factor-A molecules from the placode, also contributes to the induction of the dermal condensate. The development of the dermal condensate helps further induce the downward growth of the placode. &lt;br /&gt;
Through secreted proteins such as Sonic Hedgehog, the placode continues to proliferate and enclose the dermal condensate. This eventually forms a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings.&lt;br /&gt;
|-&lt;br /&gt;
| Peg || Sonic Hedgehog and the induction of a ‘secondary dermal signal’  (characterisation unknown) leads to a significant down-growth and proliferation of the follilular epithelium&amp;lt;ref name= PMID9768360&amp;gt;&amp;lt;pubmed&amp;gt;9768360&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
In this stage, it is also believed that the polarity of the hair follicle (the angle at which hair-follicles grow in relation to skin) and the architecture of the hair follicle itself (straight hair, wavy hair, etc) is regulated in part by Sonic Hedgehog and TGF-a signaling respectively&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|-&lt;br /&gt;
| Bulbous Peg || This stage is characterised by the appearance of the hair follicle bulb. Further and significant differentiation of the inner root sheeth and the hair shaft also characterises this stage&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The epithelial cells within the hair bulb, begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
Proteins such as Notch1 are believed to help regulate the phenotype of keratinocytes as they differentiate&amp;lt;ref name= PMID10804183&amp;gt;&amp;lt;pubmed&amp;gt;10804183&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:---|frame|right|middle|180x150px|Undifferentiated Epithelium|]]||[[Image:Fetal Hair Follicle Development - Week 8-12.JPG|frame|right|middle|180x150px|Week 8-12|]]||[[Image:Fetal Hair Follicle Development - Week 12-14.JPG|frame|right|middle|180x150px|Week 12-14|]]|| [[Image:Fetal Hair Follicle Development - Week 13-16.JPG|frame|right|middle|180x150px|Week 13-16|]] || [[Image:Fetal Hair Follicle Development - Week 19-21.JPG|frame|right|middle|180x150px|Week 19-21|]]|| [[Image:Fetal Hair Follicle Development - Week 23-28 .JPG|frame|right|middle|180x150px|Week 23-28|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:30%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:100%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Feta Nail Development - Week 9-10.jpg|frame|right|middle|135x115px|Week 9-10|]]|| [[Image:Fetal Nail Development - Week 11-12.jpg|frame|right|middle|135x115px|Week 11-12 |]] || [[Image:Fetal Nail Development - Week 13-14 .jpg|frame|right|middle|135x115px|Week 13-14|]]|| [[Image:Mature Nail .jpg|frame|right|middle|135x115px|Mature Nail|]]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{| style=&amp;quot;width:75%&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot; style=&amp;quot;text-align:center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description !! Image&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands || *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|| [[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  || Image&lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || &lt;br /&gt;
There are two major kinds of sweat glands present in humans, both of develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21.&lt;br /&gt;
Eccrine Sweat Glands&lt;br /&gt;
* Located in the skin with distributions throughout most of the body&lt;br /&gt;
* Function in thermoregulation and excretion of excess electrolytes and water&lt;br /&gt;
* Present at birth with function initiating shorting after birth&lt;br /&gt;
Apocrine Sweat Glands&lt;br /&gt;
*Located in the skin of the axilla, pubic and perianal areas and nipple areolae&lt;br /&gt;
* May function in a form of olfactory communication&lt;br /&gt;
* Present at birth with function originating at puberty&lt;br /&gt;
 &lt;br /&gt;
 || [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]] &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Video===&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
* '''1900''' - Bardeen used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study of nail development, anatomy and physiology. Thus, as such technology advances scientists have been able to uncover the morphological details of the nail and understand the changes that occur during nail development. A review of the history allows us to recognize the major contributor to this field. History of research on nail development also reveals the interesting debate on the origins of keratinized cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* German scientists Unna and Pinkus were both highly reputable dermatologists who conducted a great deal of research on the development of the skin and associated structures. They were   (&amp;lt;ref name= PMID12581143&amp;gt;&amp;lt;pubmed&amp;gt;12581143&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &amp;lt;ref&amp;gt;Roberts, H. L., &amp;amp; Walker, N. (1929). PAUL GERSON UNNA. British Journal of Dermatology, 41(4), 157-160.&amp;lt;/ref&amp;gt;)&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease. &lt;br /&gt;
* Based on their findings both scientists proposed that the nail matrix structure gives rise to the entire nail plate during normal fetal development. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|170x145px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the fetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a &amp;quot;tri-partite&amp;quot; origin of the nail plate from three tissue origins (1) the proximal nail fold (2) the matrix and (3) bed. &amp;lt;ref name= PMID5556500&amp;gt;&amp;lt;pubmed&amp;gt;5556500&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
* Prior to the 1900’s it was difficulty in obtaining normal fetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might allows us to infer the mechanism of nail plate genesis. Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate. &amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155528</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155528"/>
		<updated>2014-10-22T09:39:16Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
[[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning.&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155519</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155519"/>
		<updated>2014-10-22T09:28:50Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
[[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1-/--;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I).]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155513</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155513"/>
		<updated>2014-10-22T09:24:37Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982). Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes &amp;lt;ref&amp;gt;Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&amp;lt;/ref&amp;gt;. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Event&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*secretes vernix caseosa &lt;br /&gt;
[[Image:Newborn - vernix caseosa.jpg|frame|right|middle|250x187px|Vernix caseosa on a neonate.&amp;lt;ref&amp;gt;Image source: JazlynRoseVernixByPhilKonstantin.jpg‎ http://en.wikipedia.org/wiki/File:JazlynRoseVernixByPhilKonstantin.jpg&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Vernix caseosa is a material secreted by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*antioxidant&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*anti-infective&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*moisturises the skin&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*assists in wound-healing&amp;lt;ref name=&amp;quot;PMID19881987&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;19881987&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image:- compound mouse mutants demonstrate partially rescued upper and lower molars.png|frame|right|middle|300px|Figure 2: Msx1&amp;lt;sup&amp;gt;-/--&amp;lt;/sup&amp;gt;;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;compound mouse mutants demonstrate partially rescued upper and lower molars.]]&lt;br /&gt;
&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression (Figure 2). Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebaceous glands / Sweat glands / Mammary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==References==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155510</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155510"/>
		<updated>2014-10-22T09:19:49Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1&amp;lt;sup&amp;gt;-/--&amp;lt;/sup&amp;gt;;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference==&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
The image presented is not its entirety, only in part from the figure of the original work.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155507</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155507"/>
		<updated>2014-10-22T09:13:18Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1&amp;lt;sup&amp;gt;-/--&amp;lt;/sup&amp;gt;;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference==&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155501</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155501"/>
		<updated>2014-10-22T09:12:12Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1&amp;lt;sup&amp;gt;-/--&amp;lt;sup&amp;gt;/;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference==&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155498</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155498"/>
		<updated>2014-10-22T09:11:24Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1&amp;lt;sup&amp;gt;-/-&amp;lt;/sup&amp;gt;/;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference==&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155495</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155495"/>
		<updated>2014-10-22T09:10:54Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1&amp;lt;sup&amp;gt;-/-&amp;lt;/sup&amp;gt;/;Tbx2&amp;lt;sup&amp;gt;+/-&amp;lt;/sup&amp;gt;mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference== &amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155486</id>
		<title>File:- compound mouse mutants demonstrate partially rescued upper and lower molars.png</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:-_compound_mouse_mutants_demonstrate_partially_rescued_upper_and_lower_molars.png&amp;diff=155486"/>
		<updated>2014-10-22T09:07:59Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: Msx1-/-;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowhea...&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Msx1-/-;Tbx2+/-mouse mutants showed rescue from bud to cap phase transition in embryonic dental development. Both upper and lower molars showed an enlargement in the tooth buds (H, K, L), with few upper molars progressing to cap stage (G). The arrowheads indicate enamel knots (E,G,I). &lt;br /&gt;
&lt;br /&gt;
==Reference==&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23720046&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
© 2013. Published by The Company of Biologists Ltd. Articles published under The Company of Biologists’ Open Access model will be made freely available online via The Company’s website immediately following publication, deposited in PMC for immediate release and can be distributed under the terms of the Creative Commons Attribution (CC-BY) Licence.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155354</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155354"/>
		<updated>2014-10-22T07:34:06Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155336</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155336"/>
		<updated>2014-10-22T07:26:09Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells&amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit&amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold&amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium&amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155165</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155165"/>
		<updated>2014-10-22T05:33:39Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: /* Nail */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt;.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155150</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=155150"/>
		<updated>2014-10-22T05:17:11Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation &amp;lt;ref name= PMID1566372&amp;gt;&amp;lt;pubmed&amp;gt;1566372&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID20590427&amp;gt;&amp;lt;pubmed&amp;gt;20590427&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae &amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet&amp;lt;ref name= PMID11841536&amp;gt;&amp;lt;pubmed&amp;gt;11841536&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit. &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold. &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt; &lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium. &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
[1] &amp;lt;ref&amp;gt;Pansky, B. (1982. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502&amp;lt;/ref&amp;gt; &lt;br /&gt;
[2] &amp;lt;ref&amp;gt;Moore, K.L., Persaud, T.V.N. &amp;amp; Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders. &amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
====Sebaceous Glands====&lt;br /&gt;
*Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Mammary Glands====&lt;br /&gt;
*Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
&lt;br /&gt;
====Sweat Glands====&lt;br /&gt;
*Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs  &amp;lt;ref name= PMID19266065&amp;gt;&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&amp;lt;html5media height=&amp;quot;300&amp;quot; width=&amp;quot;400&amp;quot;&amp;gt;https://www.youtube.com/watch?v=nRH8M-arC58&amp;lt;/html5media&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
 he major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. &lt;br /&gt;
&lt;br /&gt;
* '''1958''' - Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
* '''1968''' - Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Chase and Eaton's investigated fetal hair follicle development. With key observations in understanding the cycling nature of hair follicle growth, following development. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Microscopy and staining techniques have been essential tools in study on developmental anatomy and physiology of the nail. Thus as technology advances scientists have been able to uncover the morphological changes during nail development. A review of the history allows us to recognise the major contributor to study of this field. History also reveals the interesting debate on the origins of keratinised cells which migrate to form the nail palate in weeks 20-24 of fetal development. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development - Pinkus .jpg|frame|right|middle|180x150px|Nail Plate Development - Pinkus|]]&lt;br /&gt;
&lt;br /&gt;
* '''1883''' - Unna published a chapter on the anatomy and development of the human nail in the German textbook &amp;quot;Ziemsssen's Handbuch der Speciell Pathologie und Therapie&amp;quot; - Ziemsssen 's manual of special pathology and therapy. &lt;br /&gt;
* '''1927''' - Pinkus conducted his earliest investigations into fetal nail development. His findings were published in the &amp;quot;Handbuch Der Haut und Geschlechtskrankeiten” - Manual of Skin and Venerail Disease.&lt;br /&gt;
German scientists Unna and Pinkus contributed to the understanding of the anatomy. Both scientists proposed that the structures known as the nail matrix gave rise to the entire nail plate. &lt;br /&gt;
&lt;br /&gt;
[[Image:Nail Plate Development -Lewis .jpg|frame|right|middle|160x135px|Nail Plate Development -Lewis|]]&lt;br /&gt;
&lt;br /&gt;
* '''1954''' - Barton and Lewis conducted a through investigation on the microscopic features of the foetal and mature nail and surrounding soft tissue. Lewis challenged the current thought and proposed a tri-partite origin of the nail plate from three germinative tissues (1) the proximal nail fold (2) the matrix and (3) bed.&lt;br /&gt;
Prior to the 1900’s it was difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue often damage the specimen and little detail could be seen during the microscopic examinations. Barton and Lewis conducted this investigation in hopes that a better understanding of the normal developmental anatomy and physiology would assist physicians in diagnosing and treating abnormalities. &lt;br /&gt;
&lt;br /&gt;
* '''1959''' - Samman carried out an investigation on the blood supply of the human toe nail. It was thought that a deeper understanding of morphology of the vasular supply might shed light on the genesis of the nail palate.  Samman studied the morphology and distribution of blood vessels with in the nail found capillary loops through out the nail fold and concluded that this supports the theory of multiple sites giving rise to the nail plate.  &lt;br /&gt;
&lt;br /&gt;
* '''1963''' - Zaias conducted a number of studies on the embryology of the human nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &lt;br /&gt;
* '''1968''' - Zaias and Alvazer investigated the formation of the primate nail plate. An autoradiographic study in the squirrel monkey. &lt;br /&gt;
The current understanding of fetal nail development is a summation contributions of many researches in the international scientific community. Today research continues, technology allows exploration beyond macroscopic and microscopic morphological changes in the fetal nail. Now the aim is to understand the molecular signalling with in the epidermal cells which drives this process.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt; -- Microscopic studies of fetal and mature nail and surrounding soft tissue. Lewis &lt;br /&gt;
&amp;lt;ref name= PMID14441224&amp;gt;&amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14441224&amp;lt;/pubmed&amp;gt; -- The human toe nail. Its genesis and blood supply.&lt;br /&gt;
&amp;lt;ref name= PMID6161584&amp;gt;&amp;lt;pubmed&amp;gt;6161584&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;6161584 &amp;lt;/pubmed&amp;gt; -- Ultrastructure and Growth of Human Nails &lt;br /&gt;
&amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt; -- Embryology of the Nail Zaias&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;ref name= PMID5267156&amp;gt;&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; -- &amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=154574</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=154574"/>
		<updated>2014-10-22T00:55:01Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 11===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=154565</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=154565"/>
		<updated>2014-10-22T00:53:23Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
===Lab 10===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:53, 22 October 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=153524</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=153524"/>
		<updated>2014-10-20T15:22:31Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
'''Peroxidasin is essential for eye development in the mouse:''' The precise function of peroxidasin (PXDN) during embryonic eye development is currently inadequately understood. Studies have shown that mutations in PXDN can result in severe abnormalities in the development of the cornea and the lens of the eye. Common manifestations of these abnormalities include congenital corneal opacity, cataract and glaucoma strongly associated with anterior segment dysgenesis (ASD). Recent findings suggest a complex molecular network of regulation in eye development and growth regulated through a complex series of genes and transcription factors.  Mutations in the human PXDN gene have been exhibited to cause a severe form of ASD, which involves congenital corneal opacity, cataract and glaucoma- suggesting this gene performs a vital role during the development of the eye.&lt;br /&gt;
The current study reports the first PXDN mutation in the mouse, which was produced by treatment with ENU (N-ethyl-N-nitrosourea) and produced a recessive phenotypic expression in subsequent offspring. Sequence analysis of cDNA exposed a T3816A mutation, which produced a premature stop codon (Cys1272X) in the peroxidase domain therefore affecting the enzymatic activity of the peroxidase enzyme.  A deficiency of PXDN within the mouse mutants produced eye developmental defects associated with ASD and even more severe eye defects including microphthalmia. Besides producing severe abnormalities within the eye, a key finding is that PXDN performs several functions during embryonic eye development influencing cell proliferation and differentiation as well as basement membrane consolidation. Additional affects within the mouse mutant eyes included ocular inflammation, abnormal expression of Pax6 and Foxe3 and early degenerative harm to the retina and optic nerve. &lt;br /&gt;
Stage E15.5, approximately the middle stage of development for mice was most affected, with all stages preceding this point exhibiting no gross morphological changes. It was found that Pax6, an essential gene in eye development resulted in dynamic expression changes in mutant eyes and was strongly unregulated at stage E15.5, the stage with the most significant pathological changes. A decreased cell proliferation was exhibited in the lens epithelium in comparison to the wild type mice at E14.5- E15.5 as well as a loss of integrity of the lens capsule. Together these outcomes of this study suggest that PXDN is essential for cell propagation and differentiation throughout eye developmental stages and in addition plays an important role in the consolidation of the basement membrane and in the control of ocular inflammation.  &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=153512</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=153512"/>
		<updated>2014-10-20T13:38:57Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;br /&gt;
&lt;br /&gt;
===Lab 10===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24895407&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24895407&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[Sensory - Vision Development]]&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152936</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152936"/>
		<updated>2014-10-20T03:46:22Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
- need to reference this website: http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-75-development-of-the-nails + textbook info here&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25249463&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23097355&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152912</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152912"/>
		<updated>2014-10-20T03:22:54Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
- need to reference this website: http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-75-development-of-the-nails + textbook info here&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23271751&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152891</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152891"/>
		<updated>2014-10-20T02:37:17Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
- need to reference this website: http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-75-development-of-the-nails + textbook info here&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152888</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152888"/>
		<updated>2014-10-20T02:33:42Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
*Together, fingernails and toenails are modifications of the epidermis, embryologically derived in humans from the same origin of ectodermal skin cells. &lt;br /&gt;
* Nails commence development at the tips of the digits around the stage of 10 weeks, with the initiation of fingernail growth preceding that of toenails by approximately 4 weeks. The earliest recognisable stages of nail development by week 10 are thickenings of epidermis, known as the primary nail fields, repositioning from the initial ventral surface to the eventual dorsum of each digit.&lt;br /&gt;
* The nail fields are bounded by folds of epidermis: the shallower lateral nailfolds, which adjoin into the much deeper proximal nailfold.&lt;br /&gt;
* The true nail is developed via the keratinization of cells within the proximal nailfold that proliferate over nail field, developing into the nail plate.&lt;br /&gt;
*Initially the developing nail is covered by a thin layer of epidermis, the eponychium (corneal layer of epidermis) that at later fetal stages declines to expose the free nail, however endures as the cuticle. Beneath the free end of the nail, epidermal cells aggregate to form the mass known as the hyponychium.&lt;br /&gt;
* By 32 and 36 weeks of development, the fingernails and toenails respectively reach the tips of the digits and toes. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
- need to reference this website: http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-75-development-of-the-nails + textbook info here&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152513</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152513"/>
		<updated>2014-10-19T15:25:41Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development (Figure 1). &amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently (Figure 2). Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;F5FFFA&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152507</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152507"/>
		<updated>2014-10-19T15:18:12Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|250x250px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]] || [[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152504</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152504"/>
		<updated>2014-10-19T15:10:21Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|100x 100px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice. ]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
[[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud to cap stage transition in tooth development:'''  The expression of Bmp4 is essential for the bud to cap phase transition in embryonic dental development and is accordingly firmly regulated, with earlier stages of expression localised within the dental epithelial placode developing in to a later forms of expression in the dental mesenchyme. Numerous transcription factors including Pax 9, Osr2, Barx 1, Msx1, have been identified to prompt and maintain Bmp4 expression in these critical stages of tooth development. In particular Msx1 is one such transcription factor induced through epithelial Bmp4 expression and in turn is essential for the induction and regulation of dental mesencyhmal Bmp4 expression. The results of this investigation have demonstrated the expression of an additional transcription factor, Tbx2, induced through epithelial Bmp4, within the dental mesenchyme at bud stage of dental development. To determine a functional connection between the Msx1 and Tbx2 transcription factors, a cross was made between Tbx2 and Msx1 mutant mice. The data demonstrates that bud phase tooth arrest in Msx1-/- mice is moderately restored in Msx1-/-. Tbx2+/- compound mutants. The maintenance of Tbx2 expression in the Msx-/- arrested tooth buds exhibits that the expression of Tbx2 is not dependant on that of Msx1. This restoration in the developmental process is associated with the establishment of the enamel knot (EK) and the reinstatement of mesencyhmal Bmp4 expression. Knockout of Tbx2 resulted in an increase mesencyhmal Bmp4 expression. This data demonstrates that subsequent to the induction of epithelial Bmp4, both transcription factors Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity  that results in EK formation as well as mesenchymal Bmp4 expression at the vital bud to cap phase transition in embryonic dental development resulting in appropriate morphogenesis and patterning. &amp;lt;ref name= PMID23720046&amp;gt;&amp;lt;pubmed&amp;gt;23720046&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1954 - Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID1244287&amp;gt;&amp;lt;pubmed&amp;gt;1244287&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
* Bulleted list item 1963 - Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152489</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152489"/>
		<updated>2014-10-19T12:53:41Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|100x 100px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice. ]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
[[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152486</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152486"/>
		<updated>2014-10-19T12:50:30Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|100x 100px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
[[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152483</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152483"/>
		<updated>2014-10-19T12:45:16Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
[[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152480</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152480"/>
		<updated>2014-10-19T12:41:32Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
[[Image: Screen Shot 2014-10-19 at 11.09.42 PM.png|frame|right|middle|300px|Figure 2: The expression of stem cell marker, nestin and and proliferative marker, Ki67 in the developing human nail.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152468</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152468"/>
		<updated>2014-10-19T12:16:09Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152465</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152465"/>
		<updated>2014-10-19T12:12:53Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152462</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152462"/>
		<updated>2014-10-19T12:09:59Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' In comparison to the characterization of the stem cell niche within the folliculosebaceous-apocrine unit, the local microenvironment of stem cells within the human nail organ is yet to be characterized. The aims of the current study was through immunohistochemical analysis to describe the expression pattern of six follicular stem cell markers; cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK-19), PHLDA1, CD200 and nestin within the developing human nail and compare it with the embryonic and fetal human hair follicle. In addition, locations of vast proliferative activity within the nail were assessed using labeling with Ki-67.  The stem cell markers CK15 (both clones), CK19, PHLDA1, CD200 and nestin showed no staining within the nail and hair matrix samples, however were present within the central proximal nail fold and follicular bulge. The biochemical marker for proliferation, Ki-67 showed the highest concentration of proliferative cells within the hair germ, lower regions of the hair peg and in the hair matrix. In the developing human nail the expression of Ki-67 was most prominent within the nail bed epithelium and the later nail matrix. In contrast the lowest numbers of kI-67 positive staining cells were located in regions of stem cell niches of the follicular bulge and proximal ventral nail fold as stem cells divide infrequently. Throughout the course of embryonic development these stem cell markers exhibit a highly specific expression pattern both within the nail and the hair follicle. The results seem to suggest that during embryonic envelopment the proximal ventral nail fold is the niche for nail stem cells.  &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Prior to the 1950’s there had not been a great deal of research into the area of foetal nail development. This was primarily due to the difficulty in obtaining normal foetal specimens. Furthermore, the histological staining techniques used to prepare slides of nail tissue, required prolonged periods of decalcification. This process often damage the specimen and little detail could be seen during the microscopic examinations. As a result, the histological features and developmental stages of the nail could not be deduced. From a clinical perspective, the incomprehensive understanding the &amp;quot;normal nail&amp;quot; features made it difficult for dermatologists to correctly diagnose abnormalities. &amp;lt;ref name= PMID13206419&amp;gt;&amp;lt;pubmed&amp;gt;13206419&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was in 1954 that Barton and Lewis conducted a through microscopic examination of foetal and adult nail. It is clear that Barton and Lewis conducted an investigation with one underlying aim. They hoped that a through understanding of the normal development, anatomy and physiology would assist physicians in diagnosing and treating abnormalities.  A number of key features in nail anatomy were identified and named. The Nail Plate, Nail Root, underlying Nail Bed, Eponychium and Hyponychium. &amp;lt;ref name= PMID -- &amp;gt;&amp;lt;pubmed&amp;gt;--&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
In 1963 Nardo Zaias conducted a study on the Embryology of the Human Nail. This investigation contributed to our understanding of different stages in foetal nail development. Zaias studied an number of foetal specimens at different stages in development. As a result, Zaias was able to propose a rough timeline highlighting morphological hallmarks in normal nail development. &amp;lt;ref name= PMID14003041&amp;gt;&amp;lt;pubmed&amp;gt;14003041&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Header text !! Header text&lt;br /&gt;
|-&lt;br /&gt;
| Week 9 || The primitive nail beings to from&lt;br /&gt;
|-&lt;br /&gt;
| Week 10|| The primary nail field is establish&lt;br /&gt;
|-&lt;br /&gt;
| Week 11 || Distal ridges of nail bed keratinise. &lt;br /&gt;
|-&lt;br /&gt;
| Week 13 || Early nail matrix. &lt;br /&gt;
|-&lt;br /&gt;
| Week 20 || Nail plate begins to grow over the nail bed.&lt;br /&gt;
|-&lt;br /&gt;
| Week 24 || Free nail plate is visible to the naked eye.&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
Today research into the field of foetal nail development continues. Technology allows exploration beyond staging the macroscopic and microscopic morphological changes. We are now able to understand the molecular signalling with in the epidermis which drives this process.&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152396</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152396"/>
		<updated>2014-10-19T08:29:40Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152390</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152390"/>
		<updated>2014-10-19T08:11:51Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152372</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152372"/>
		<updated>2014-10-19T07:51:27Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and in particular, the development of hair follicles (HF). The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis during the primary stages of mouse hair follicle development through the investigation of the precise expression patterns and role of the Cxcr4 receptor in two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Staining patterns of the Cxcr4 receptor in the budding HF revealed a high concentration within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested through Cxcr4 receptor ablation in both the mesenchymal and epithelial layers of the developing embryonic skin of conditional knockout mice (cKO) and was verified through immunofluorescence staining techniques. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups demonstrating that the chemokine signalling through the Cxcr4 receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;gt;&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152366</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152366"/>
		<updated>2014-10-19T07:18:51Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and its related appendages. In particular, the development of hair follicles (HF) has been identified to be critically associated with the synchronized signalling exchanges between these two cellular layers and this interaction is understood to involve two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Expression of the chemokine receptor Cxcr4 has recently been detected in DC’s of budding HF’s however its function in supporting embryonic HF morphogenesis is currently unidentified. The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis through investigating the precise expression patterns and subsequent role of the Cxcr4 receptor in both DC and epithelial placode cells during the primary stages of mouse hair follicle development. Expression patterns of the Cxcr4 receptor were identified via immunofluoresent staining on back skin sections of mouse embryos aged 14.5 days during the three main HF developmental stages. Subsequent analysis of staining patterns revealed Cxcr4 receptor expression in budding HF is concentrated within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested using a separate cre/loxP recombination system in genetically altered mice to conditionally ablate this gene in both the mesenchymal and epithelial layers of the developing embryonic mouse skin. To target DC’s a cross was made between Tbx18cre and Cxcr4 floxed mice and epithelial placodes were targeted via the crossing of Krt12-cre with Cxcr4 floxed mice. Cxcr4 receptor ablation in conditional knockout mice (cKO) was verified through immunofluorescence. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups showed that the Cxcr4 receptor and the associated chemokine signalling through this receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152363</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152363"/>
		<updated>2014-10-19T07:14:23Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and its related appendages. In particular, the development of hair follicles (HF) has been identified to be critically associated with the synchronized signalling exchanges between these two cellular layers and this interaction is understood to involve two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Expression of the chemokine receptor Cxcr4 has recently been detected in DC’s of budding HF’s however its function in supporting embryonic HF morphogenesis is currently unidentified. The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis through investigating the precise expression patterns and subsequent role of the Cxcr4 receptor in both DC and epithelial placode cells during the primary stages of mouse hair follicle development. Expression patterns of the Cxcr4 receptor were identified via immunofluoresent staining on back skin sections of mouse embryos aged 14.5 days during the three main HF developmental stages. Subsequent analysis of staining patterns revealed Cxcr4 receptor expression in budding HF is concentrated within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested using a separate cre/loxP recombination system in genetically altered mice to conditionally ablate this gene in both the mesenchymal and epithelial layers of the developing embryonic mouse skin. To target DC’s a cross was made between Tbx18cre and Cxcr4 floxed mice and epithelial placodes were targeted via the crossing of Krt12-cre with Cxcr4 floxed mice. Cxcr4 receptor ablation in conditional knockout mice (cKO) was verified through immunofluorescence. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups showed that the Cxcr4 receptor and the associated chemokine signalling through this receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152360</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152360"/>
		<updated>2014-10-19T07:10:53Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands. &amp;lt;ref name=PMID23377137&amp;gt;&amp;lt;pubmed&amp;gt;23377137&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and its related appendages. In particular, the development of hair follicles (HF) has been identified to be critically associated with the synchronized signalling exchanges between these two cellular layers and this interaction is understood to involve two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Expression of the chemokine receptor Cxcr4 has recently been detected in DC’s of budding HF’s however its function in supporting embryonic HF morphogenesis is currently unidentified. The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis through investigating the precise expression patterns and subsequent role of the Cxcr4 receptor in both DC and epithelial placode cells during the primary stages of mouse hair follicle development. Expression patterns of the Cxcr4 receptor were identified via immunofluoresent staining on back skin sections of mouse embryos aged 14.5 days during the three main HF developmental stages. Subsequent analysis of staining patterns revealed Cxcr4 receptor expression in budding HF is concentrated within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested using a separate cre/loxP recombination system in genetically altered mice to conditionally ablate this gene in both the mesenchymal and epithelial layers of the developing embryonic mouse skin. To target DC’s a cross was made between Tbx18cre and Cxcr4 floxed mice and epithelial placodes were targeted via the crossing of Krt12-cre with Cxcr4 floxed mice. Cxcr4 receptor ablation in conditional knockout mice (cKO) was verified through immunofluorescence. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups showed that the Cxcr4 receptor and the associated chemokine signalling through this receptor is inessential for normal early HF development.&amp;lt;ref name= PMID25066162&amp;gt;&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:''' &amp;lt;ref name= PMID22804461&amp;gt;&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:''' &amp;lt;ref name= PMID19878652&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152354</id>
		<title>2014 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2014_Group_Project_5&amp;diff=152354"/>
		<updated>2014-10-19T06:55:20Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014header}}&lt;br /&gt;
=Integumentary=&lt;br /&gt;
==Introduction==&lt;br /&gt;
This page concerns the development of the integumentary system in the fetal stage of development, particularly its organs i.e. the skin, glands, hair, teeth, and nails. It explores the mechanism of development as well as the timeline of development. This page also outlines some recent findings on the development of the integumentary system, as well as historic findings. Finally, this page also explores some of the congenital abnormalities of the integumentary system, its mechanism or pathogenesis, clinical manifestations, and how they are treated or managed.&lt;br /&gt;
&lt;br /&gt;
==Development Overview==&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The skin consists of 2 layers: the outer layer (epidermis) and a deeper connective tissue layer (dermis). &lt;br /&gt;
*The epidermis is derived from the ectoderm. Initially it exists as only a single layer of ectodermal cells at 7-8 days of gestation. However, by about 13-14 weeks after gestation, a 3- layered structure of fetal epidermis exists- consisting of the stratum basale, 1 or 2 intermediate layers and the periderm. The peridermal cells eventually become desquamated and form part of the vernix cervix.&lt;br /&gt;
** The 5 definitive layers of the adult skin are evident in the human fetus after 22-24 weeks of gestation. Indirect influences form the dermis help differentiate the epidermis into: stratum basale, stratum spinosium, stratum granulosum, stratum lucidum and stratum corneum. &lt;br /&gt;
*The somatic mesoderm is the embryonic origin of the dermis. The mesoderm of the dermatones of the body, also contribute to the development of the dermis. Specifically though, in the head and neck region of the body, the dermis is derived from neural crest cells.&lt;br /&gt;
** The dermis is initially composed of just mesenchymal cells- loosely aggregated mesodermal cells. These mesenchymal cells later develop into fibroblasts- which function to secrete collagen and lay-down elastic fibers  into the extracellular matrix. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
3 other specialised cells of the epidermis also exists- these include melanoblasts, Langherhan cells and Merkel cells.&lt;br /&gt;
*Melanoblasts- are derived from neural crest cells that have migrated into the stratum basale. Mid-pregnancy, melanosomes are observed, differentiating the melanoblasts into melanocytes&lt;br /&gt;
*Langheran cells- are derived from bone marrow (originally form mesoderm) and migrate into the epidermis. They have the function of antigen presentation.&lt;br /&gt;
*Merkel cells- still have an uncertain origin. They have a function related to mechanoreception.&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:60%; height:125px&amp;quot; border=&amp;quot;1&amp;quot; align=&amp;quot;center&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Week !! Description !! Phase Diagram &lt;br /&gt;
|-&lt;br /&gt;
| Week 6-8|| In an electron micrograph study of the epidermis, the periderm and and basal layer of the developing skin was observed.  || [[Image:Human_embryo_skin_8-9_week_EGA.jpg|100x100px|Weeks 6-8]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 7-9 || In an electron micrograph study of the epidermis at weeks 7-9 of development, the stratified three-layer structure of the epidermis was observed. Kertain filaments have been encircled. || [[Image:Human_embryo_skin_9-11_week_EGA.jpg|100x100px| Weeks 7-9]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 14 || By week 14, the basal layer, the intermediate layer/s and the periderm 3-layered structure can be observed in the fetus. By week 14, K17 can also be found in the basal and intermediate layers of the epidermis (In adult skin, K17 was not observed) || [[Image:Fetal_integumentary_histology_14w.jpg|100x100px| Week 14]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 16 || In a study, by week 16, developing blood vessels were observed. CD31 and a sub-type of smooth-muscle actin stained positive in these observed developing blood vessels. || [[Image:Inaugumentary_week16.jpg|100x100px| Week 16]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 18 || Example || [[Image:542px-Fetal_integumentary_histology_18.jpg|100x100px| Week 18]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 19 || In a study, by week 19, as opposed to week 14, K17 was found present in the basal, intermediate and periderm layers. K17 also stained positive in the developing hair follicles. || [[Image:Inaugumentary-_Week_19.jpg|100x100px| Week 19]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 20  || By week 20, hair follicles can be already be seen in the epidermis. The total number of intermediate layers has also increased || [[Image:Fetal_integumentary_histology_20.jpg|100x100px|Week 20]]&lt;br /&gt;
|-&lt;br /&gt;
| Week 22 || In an electron micrograph study at week 22 of development, kertanised epidermis was analysed. It was observed that glycogen was abundantly present throughout all epidermal layers. The included arrows, highlight the keratin filament bundles, which are now organised and peripherally placed. || [[Image:Human_embryo_skin_24_week_EGA.jpg|100x100px| Week 22]]&lt;br /&gt;
|-&lt;br /&gt;
| Adult|| In adult skin- a greater diversity of cells can be seen as more cells differentiate. Basal, spinous, granular and cornified cells are all example of such. In another study, chondroitin sulphate was observed in the basement membrane zone of the adult epidermis. In the same study,  chondroitin sulphate was only observed towards the upper-part of the dermis. Also, elastin was present in the adult specimens, but not in the earlier fetal samples.  || [[Image:Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]] [[Image:542px-Fetal_integumentary_histology_Adult.jpg|100x100px| Adult]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19701759&amp;lt;/pubmed&amp;gt;  &lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC2113922&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
{|  align=&amp;quot;center&amp;quot; style=&amp;quot;width:70%; height:200px&amp;quot; border=1&lt;br /&gt;
|-&lt;br /&gt;
! Gland Type !! Description&lt;br /&gt;
|-&lt;br /&gt;
| Sebaceous Glands|| *Sebaceous glands develop from the epithelial wall of the hair follicle.&lt;br /&gt;
*Vernix caseosa &lt;br /&gt;
Vernix caseosa is a material produced by sebaceous glands in the foetus in the last trimester of development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; and is characterised by it’s cheese-like appearance around the neonate at birth. The functions of vernix caseosa include:&lt;br /&gt;
*thermal regulation &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*barrier to water loss (to keep fetal skin hydrated)&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*acid mantle development &amp;lt;ref name=&amp;quot;PMID15830002&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;15830002&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*prevents the epidermis from water contact while epidermal cornification and formation of the stratum corneum occurs&amp;lt;ref name=&amp;quot;PMID21504444&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21504444&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| Mammary Glands || *Mammary glands develop from the mammary ridge- a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). This occurs at about week 6 of development. Prior to puberty, the mammary glands are anatomically indistinguishable.  &lt;br /&gt;
|-&lt;br /&gt;
| Sweat Glands || *Eccrine and apocrine sweat glands develop from the downgrowths of the epidermis into the underlying dermis. It has been seen and detected in studies from week 21. &lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
    &lt;br /&gt;
&lt;br /&gt;
{| style=&amp;quot;width:40%; height:170px&amp;quot; align=&amp;quot;center&amp;quot; &lt;br /&gt;
|-&lt;br /&gt;
| [[Image:Integumentary_histology_02.jpg|frame| 250x250px|Histology of eccrine sweat gland]]  ||  [[Image:Integumentary-_sebaceous_gland_histology_01.jpg|frame|centre|250x250px|Histology of sebaceous gland]]&lt;br /&gt;
|} &lt;br /&gt;
&lt;br /&gt;
::: Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Gland Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Gland_Development&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
[[Image:Hair_development_stages.jpg|frame|right|middle|300x250px|The stages of hair development]]&lt;br /&gt;
&lt;br /&gt;
Hair originates from the ectoderm. At about 12 weeks, it is believed that specific signals from the dermis  begin to induce hair follicle formation. Through reciprocal interactions, cells from the stratum basale grow into the underlying dermis. The epithelial cells influenced by these dermal signals, develop a placode- a thickening of the columnar cells. Signalling from the placode than leads to the development of a dermal condensate, which further induces the downward growth of the placode. The hair follicle, continues to proliferate and enclose the dermal condensate, forming a deep, club-shaped hair bud, with an invaginated dermal papillae. These dermal papillae are rapidly infiltrated by blood vessels and nerve endings. The epithelial cells within the hair bulb, then begin to differentiate into the germinal matrix – which grow, proliferate and keratinise to form the hair shaft and internal root sheet. Other epithelial cells outside of the hair bud, form the external hair sheeth. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheeth and the arrecrtor pili muscles for hairs.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;20590427 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;11841536 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;1566372 &amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
* Nails also develop from the epidermis. &lt;br /&gt;
* The development and growth of the fingernails occurs earlier in week 10, compared to the toe nails- which only start developing in week 14.  &lt;br /&gt;
* Nail development grows first on the tips of the digits, before actually migrating,-with their innervation-onto the dorsal surface. Nails reach the digit fingertips at approximately week 32, while for toenails, it occurs a bit later- at week 36.&lt;br /&gt;
* The nail fold is thickened epidermis, with keratinisation of the proximal end forming the nail plate&lt;br /&gt;
&lt;br /&gt;
:::Cite this page: Hill, M.A. (2014) Embryology Integumentary System - Nail Development. Retrieved October 7, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_-_Nail_Development&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&lt;br /&gt;
The ectoderm and the associated underlying layer of neural crest cells, are the origin for teeth development. As the oral epithelium grows and proliferates, it has a downward movement into the underlying neural crest layer. This leads to the formation of the dental lamina. These dental lamina, then,  gives rise to tooth buds. These tooth buds, later form and develop into enamel organs. With further development, these enamel organs  give rise to ameloblasts- which produce enamel. The dental papilla, on the other hand is formed by the neural crest cells which underlie the enamel organs. These dental papillae than give rise to the dental pulp and odontoblasts- which produce predentin and dentin, in the adult body.&lt;br /&gt;
&lt;br /&gt;
[[Image:Tooth development stage.jpg|frame|left|middle|425x300px|The stages of embryonic teeth development]] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;wikitable&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
! Stage!! Week !! Description &lt;br /&gt;
|-&lt;br /&gt;
| (A) Lamina|| Week 6 || The oral ectoderm, closely interacts with the neural crest ectomesenchyme. In the Lamina stage, teeth may grow only within the epithelium.&lt;br /&gt;
|-&lt;br /&gt;
| (B) Placode|| Week 7 || The dental lamina and and the dental placodes arise, due to specific signals from adjacent epithelial cells&lt;br /&gt;
|-&lt;br /&gt;
| (C) Bud || Week 8 || Tooth buds are formed, as the epithelium cells interact with the messenchyme. This occurs at the sides of the dental placodes. Also, as opposed to the earlier Lamina stage, in the Bud stage, teeth may now only grow within the ectomesenchyme&lt;br /&gt;
|-&lt;br /&gt;
| (D) Cap|| Week 11 || After folding, the bud takes upon the shape of an inverted cap&lt;br /&gt;
|-&lt;br /&gt;
| (E) Bell|| Week 14 || The bud refolds once again, this time taking upon the shape of a bell&lt;br /&gt;
|}&lt;br /&gt;
  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19266065&amp;lt;/pubmed&amp;gt;| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&amp;amp;tool=pmcentrez PMCID: PMC2651620]&lt;br /&gt;
&lt;br /&gt;
Int J Biol Sci. 2009; 5(3): 226–243.&lt;br /&gt;
Published online 2009 February 24.&lt;br /&gt;
&lt;br /&gt;
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.&lt;br /&gt;
&lt;br /&gt;
==Some Recent Findings==&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development:''' In recognition of the vital roles of CASP-14 and CK-19 in human skin development and maturation, the purpose of this study was to primordially investigate the expression of these two molecular factors throughout the stages of human fetal skin development from gestation to the postnatal period in order to evaluate their singular and collective functions in epidermal and associated appendage maturation and processes of differentiation and re-modelling of human fetal skin. The results of the immunohistochemical study showed the expression of CASP-14 to be a biochemical marker of human epithelial differentiation during gestation, whilst CK-19 was a marker for epidermal stem cells nests of the stratum basale of the fetal epidermis and appendages. CASP-14 was concentrated within the more differentiated fetal epidermal layers, progressively declining from the basal layer toward term whilst CK-19 showed reduced expression with progressive epidermal development of the fetal stages and was a biochemical marker for epidermal stem cells nests of the stratum basale showing marginal conservation in basal cell nests at term and postnatally. Expression of CASP-14 within the epidermal appendages of the hair follicles and sebaceous glands were concentrated within the greater differentiated inner root sheath whilst CK-19 was greatly concentrated within the outer root sheath. Inconsistent patterns of expression of both molecules CASP-14 and CK-19 were demonstrated within eccrine sweat glands.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 23377137&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
[[Image: Eosin_staining_of_mouse_embryonic_skin.png|frame|right|middle|300px|Figure 1: Hematoxylin/ eosin staining of embryonic skin sections and macroscopic view of external hair shafts of mouse. Cxcr4 receptor ablation in condensates and placodes show no effect on mouse HF morphogenesis. Hair follicle and shaft develop normally and in comparable numbers in both Tbx18cre (a) and Krt14-cre (b) Cxcr4fl/fl cKO mice.]]&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation:''' Cellular signalling between mesencyhmal and epithelial layers of the developing skin initiate an assortment of morphogenetic events throughout embryogenesis, involving the formation of the skin and its related appendages. In particular, the development of hair follicles (HF) has been identified to be critically associated with the synchronized signalling exchanges between these two cellular layers and this interaction is understood to involve two specialised cell types- mesenchymal dermal condensate (DC) cells and epithelial placode cells. Expression of the chemokine receptor Cxcr4 has recently been detected in DC’s of budding HF’s however its function in supporting embryonic HF morphogenesis is currently unidentified. The aims of this study was to identify the specific signalling pathways associated with HF morphogenesis through investigating the precise expression patterns and subsequent role of the Cxcr4 receptor in both DC and epithelial placode cells during the primary stages of mouse hair follicle development. Expression patterns of the Cxcr4 receptor were identified via immunofluoresent staining on back skin sections of mouse embryos aged 14.5 days during the three main HF developmental stages. Subsequent analysis of staining patterns revealed Cxcr4 receptor expression in budding HF is concentrated within epithelial placode cells and later DC cells in developing HF’s, signifying a shift of expression between epithelial and mesenchymal layers during HF morphogenesis. The functionality of the Cxcr4 receptor was tested using a separate cre/loxP recombination system in genetically altered mice to conditionally ablate this gene in both the mesenchymal and epithelial layers of the developing embryonic mouse skin. To target DC’s a cross was made between Tbx18cre and Cxcr4 floxed mice and epithelial placodes were targeted via the crossing of Krt12-cre with Cxcr4 floxed mice. Cxcr4 receptor ablation in conditional knockout mice (cKO) was verified through immunofluorescence. Normal HF development was still induced despite the absence of Cxcr4 expression in the skin of the cKO mice and numbers were comparable to those found in the wild-type (WT) control group in embryonic and postnatal skin groups showed that the Cxcr4 receptor and the associated chemokine signalling through this receptor is inessential for normal early HF development.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25066162&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin:'''&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22804461&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
{|&lt;br /&gt;
|-bgcolor=&amp;quot;DDCEF2&amp;quot;&lt;br /&gt;
|&lt;br /&gt;
* '''WNT5A inhibits human dental papilla cell proliferation and migration:'''&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;19878652&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
{| class=&amp;quot;wikitable mw-collapsible mw-collapsed&amp;quot;&lt;br /&gt;
! More Recent Papers&lt;br /&gt;
|-&lt;br /&gt;
|&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23826487&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;22342389&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24911066&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25143675&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
==Historic Findings==&lt;br /&gt;
&lt;br /&gt;
Knowledge of the Integumentary expands in conjunction with technological developments that allow observation of microscopic structures. Historically animal models have been used to map the stages in the development of the fetal integumentary system.&lt;br /&gt;
&lt;br /&gt;
===Skin===&lt;br /&gt;
&lt;br /&gt;
In 1900 Bardeen C. R  used the pig animal model to study the histogenesis of the dermomyotomes and nervous appratus. Bardeen and other scientists established that the human skin results from the union of the epithelial material derived from the ectoderm (epidermis) and the connective tissue origination from the mesoderm (dermis). &lt;br /&gt;
&lt;br /&gt;
http://journals.lww.com/plasreconsurg/Citation/1949/07000/CLINICAL_ASPECTS_OF_EMBRYOLOGICAL_SKIN.8.aspx &lt;br /&gt;
Bardeen, C. R. (1900). The development of the musculature of the body wall in the pig, including its histogenesis and its relations to the myotomes and to the skeletal and nervous apparatus. Johns Hopkins Hosp. Rep, 9, 367-399.&lt;br /&gt;
&lt;br /&gt;
===Glands===&lt;br /&gt;
&lt;br /&gt;
Sebacious glands / Sweat glands / Mamailliary&lt;br /&gt;
&lt;br /&gt;
In the 1968 Robins and Breathnatch investigated the development on the sebacious and apocrine swelling in the skin, which where closely associated with development of the hair follicle. They observed differentiation of desmosomes and development of cytoplasmic contents of the cell. &lt;br /&gt;
&lt;br /&gt;
===Hair===&lt;br /&gt;
&lt;br /&gt;
STRUCTURE : The major anatomic details of hair development in the human foetus have been established by studies with light microscopy. Electron microscopy was not commonly used to until recently and so little was known about the ultrastructure of the skin. Over the past few years, reports have been published on the epidermal melanocytes and periderm. In 1968 Breathnach and Smith determined the fine structure of the cells of follicle and dermal papilla in the first two weeks of fetal development.  The Peripheral Nerves, the sweat duct and nail development were also explored and the interrelationship of cells at particular foetal stages was deduced. These studies, and other laboratory animals, have provided information on the differentiation of cells and tissue of some functional importance and underline the role of cells and tissues.&lt;br /&gt;
&lt;br /&gt;
DEVELOPMENT:  In 1958 Pinkus established the following stages of fetal hair follicle development: pre-germ, hair-germ, hair-peg,andbulbous-peg stages. Pinkus also determined that the developed hair fibres grow through the epidermis and appears at the level of the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
Robertson, J. R. (Ed.). (2002). Forensic examination of hair. CRC Press.&lt;br /&gt;
&lt;br /&gt;
The mechanism of fetal hair follicle development was noted to be a cycling phenomenon in 1959 by Chase and Eaton's experiments. Development begins with the downwards growth of the follicle structure from the level of the dermis. The follicle is a processes during the quiecent phase thought he adipose layer during gowth and differntiation. They also established that upward movement of hair inovlves the addition of next cells from the matrix of the follicle and an enlargement of each cell. Furthermore their research also showed that the epidermal and dermal layers were dynamic and interacting with each other. The most significant developments in the understanding of hair follicle development came from studies investigating the differentiation pattern of cells as the follicle develops. &amp;lt;ref name= PMID5656140&amp;gt;&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5656140&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&amp;lt;pubmed&amp;gt;4097391&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Determined that the hair fibre finally breaks through the epidermis and appres about the skin at around 19-21 weeks of development. The lanugo (foetal) hair is extremely fine with no medulla and a tip free of pigment. &lt;br /&gt;
&lt;br /&gt;
===Nail===&lt;br /&gt;
&lt;br /&gt;
Until 1954 There was no through anatomic study on the development of the normal nail. This is because obtaining normals specimines and histological techniques required prolonged decalcification, with nitric acid because of the decalcification of histological specimens were often damaged. &lt;br /&gt;
&lt;br /&gt;
===Teeth===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;5267156&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
===Aplasia Cutis Congenita===&lt;br /&gt;
[[Image:Cutis aplasia.jpg|frame|right|middle|250x187px|Aplasia cutis congenita at the scalp]]&lt;br /&gt;
Aplasia cutis congenita (ACC) is a rare skin abnormality, characterised by the absence of all layers of the skin. It is most common to occur on the scalp (70%), specially the vertex.  In severe cases, the defect can go as deep as the bone or the dura. Other sites of ACC include the skin of the limb regions. “ACC occurs in approximately 1 in 10000 live births, with a female-to-male ratio of 7:5.” The specific aetiologic agent for ACC is still unknown. It has been suggested to be genetic and/or environmental. The damage to the vertex is suggested to be the result of the biomechanical stretch at this area when the fetal brain is growing.&amp;lt;ref name= PMID22549580&amp;gt;&amp;lt;pubmed&amp;gt;22549580&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Presently, ACC is managed via conservative treatments or surgical treatments. Conservative treatments refer to basic wound treatments and preventing infection with the use dressings and antibiotics. Surgical treatments, specifically scalp reconstruction procedures, aim to reconstruct the damage to the skin through skin grafts, local scalp flaps, and pericardial scalp flaps. Large defects are often treated using surgical treatments.&amp;lt;ref name= PMID23147310&amp;gt;&amp;lt;pubmed&amp;gt;23147310&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Dystrophic Epidermolysis Bullosa===&lt;br /&gt;
[[Image:Dystrophic Epidermolysis Bullosa lesions.jpg|frame|right|sub|270x230px|Severe skin lesions due to Dystrophic epidermolysis bullosa.&amp;lt;ref name=&amp;quot;PMID23739692&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23739692&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Dystrophic Epidermolysis Bullosa (DEB), a type of epidermolysis bullosa, is a genetic disease of the skin, usually present at birth or at an early age&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Currently, around 400,000 - 500,000 people are affected with the disease&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is characterised by the fragility of the skin&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, where it blisters upon minimal trauma and scars&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, usually at the extremities&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. It is caused by a mutation in collagen VII gene (COL7A1)&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, which is responsible for the the formation of anchoring fibrils&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Anchoring fibrils are responsible for dermal-epidermal adherence&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, that is why it’s loss of function results to blistering of the skin. In some cases, even teeth and nails are affected. Teeth of patients with DEB have enamel defects and when combined with poor oral hygiene, it may lead to decay. Nails of DEB patients are often dystrophic and will eventually be lost.&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There are currently no known cures for DEB; however there are techniques to manage the clinical manifestations of the disease, which include:&lt;br /&gt;
*wound care&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*preventing factors that may cause blistering&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*using aqueous disinfectants - highly effective&amp;lt;ref name= PMID19945622&amp;gt;&amp;lt;pubmed&amp;gt;19945622&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*dental care&amp;lt;ref name= PMID252845240&amp;gt;&amp;lt;pubmed&amp;gt;25284524&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;:&lt;br /&gt;
:-use of topical fluoride&lt;br /&gt;
:-careful prophylaxis&lt;br /&gt;
:-use of topical antibiotics to prevent secondary infections&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubme&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
One study is currently exploring the potential of protein therapy as a treatment for DEB. Their results show that intradermal injection of recombinant human collagen 7 in mice with DEB led to “restoration of C7 and anchoring fibrils.”&amp;lt;ref name= PMID19018253&amp;gt;&amp;lt;pubmed&amp;gt;19018253&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Other techniques that aim to restore C7 include:&lt;br /&gt;
*bone marrow transplant- improved blistering in mice specimen and increase survival rates&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*hematopoietic cell transplant (HCT)- increased deposition of C7 in injured skin&amp;lt;ref name= PMID24860657&amp;gt;&amp;lt;pubmed&amp;gt;24860657&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Congenital Alopecia Areata===&lt;br /&gt;
[[Image:Alopecia Areata.jpg|frame|right|middle|270x220px|Patches of hair loss: a sign of alopecia areata.&amp;lt;ref name=&amp;quot;PMID23960401&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23960401&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Alopecia areata (AA) is an abnormality of the hair affecting anagen hair follicles, characterised by well-demarcated patches of hair loss. It is non-scarring and can occur on the scalp and/or the body. 90% of AA cases occur on the scalp. 5%-10% of patients with AA lose all hair on their scalp; this is called alopecia totalis. While others lose all of their body hair, this is called alopecia universalis. &amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Its pathogenesis is considered to be both genetic and autoimmune. There is an abnormality with the genes related to the immune system and to the hair follicles. And histopathology shows signs of lymphatic infiltration of the hair follicles and the loss of these scalp lymphocytes allow hair follicles to recover.&amp;lt;ref name= PMID16338213&amp;gt;&amp;lt;pubmed&amp;gt;16338213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; High frequencies of catagen and telogen hair follicles are also present in areas affected by AA.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
There is currently no cure for AA. There are several treatments to combat AA but none of these have led to remission of the disease, the most effective being corticosteroids and topical immunotherapy.&amp;lt;ref name= PMID17269961&amp;gt;&amp;lt;pubmed&amp;gt;17269961&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; A new method of treating alopecia areata is currently being studied. Transepidermal drug delivery (TED) is a new treatment that functions by creating micro-channels in the epidermis. By doing so, drug delivery to the skin is improved. This treatment was highly effective and had lower rates of side effects, e.g. pain, compared to previous treatments.&amp;lt;ref name= PMID25260052&amp;gt;&amp;lt;pubmed&amp;gt;25260052&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Harlequin Ichthyosis===&lt;br /&gt;
[[Image:Harlequin Ichthyosis.jpg|frame|right|middle|250x200px|A baby with harlequin ichthyosis.&amp;lt;ref name=&amp;quot;PMID24520234&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520234&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Congenital ichthyosis is an autosomal recessive disease of the skin, characterised by visible and excessive scaling of the skin and hyperkeratosis, i.e. thickening of stratum corneum layer of the epidermis and in some cases, hypohidrosis, i.e. the lack of ability to sweat. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Harlequin ichthyosis (HI) occurs only in 1 in 1,000,000 babies. It is life-threatening in the first few weeks and/or months of the neonate.&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; The thick skin can restrict movement of the baby and sometimes constrict extremities and lead to necrosis then autoamputation.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Babies with HI are also characterised by bilateral ectropion (everted eyelids), eclabium (everted lips), and underdeveloped nose.&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; In 50% of HI cases, respiratory failure is often the cause of death.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; This disease is caused by a nonsense mutation in the ATP-binding-cassette A12 (ABCA12) gene, which is responsible for encoding a lipid transporter essential for the regulation of lamellar bodies. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID23419760&amp;gt;&amp;lt;pubmed&amp;gt;23419760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no known cure for this disease. Management techniques include:&lt;br /&gt;
*Monitoring in neonatal intensive care units. &lt;br /&gt;
:-Temperature within the incubator is controlled to avoid fluctuation in body temperature and to stop sweating. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Mechanical removal of excess scales from the skin &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Bathing to remove excess scales from the skin&amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
*Topical therapy - to reduce hyperkeratosis. &amp;lt;ref name= PMID19824737&amp;gt;&amp;lt;pubmed&amp;gt;19824737&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
*Use of oral retinoids - known to have high rates of survival.&amp;lt;ref name= PMID24124810&amp;gt;&amp;lt;pubmed&amp;gt;24124810&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Hypohidrotic Ectodermal Dysplasia===&lt;br /&gt;
[[Image:Oligodontia.jpg|frame|right|middle|250x187px|Oligodontia: a clinical manifestation of HED.&amp;lt;ref name=&amp;quot;PMID21165248 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21165248 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
Hypohidrotic ectodermal dysplasia (HED) is the most of all ectodermal dysplasias, caused by an abnormality in the development of ectodermal tissues, which inlude skin, hair, teeth, sweat glands, and nails.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Patients with ectodermal dysplasia often have sparse hair and oligodontia, which is a condition where teeth are missing and are poorly developed.&amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; Sweating is a very important function in the body in terms of thermoregulation. HED is mainly characterised by hypohidrosis due to the lack of sweat glands in the skin, which could lead to hyperpyrexia and sometimes death.  In neonates, the mortality rate of HED reaches up to 30%, with the first year of life having the highest risk. &amp;lt;ref name= PMID20682465&amp;gt;&amp;lt;pubmed&amp;gt;20682465&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; HED is caused by a genetic abnormality of the ectodysplasin A gene (EDA) and passed on by X-linked inheritance. The mutations of this gene results in the poor sweating ability or none at all in a person. The effects of this abnormality is usually more severe in males than in females. &amp;lt;ref name= PMID21357618&amp;gt;&amp;lt;pubmed&amp;gt;21357618&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
There is currently no pharmacological therapies for HED but there are methods applied to prevent the disease from aggravating. Neonates with HED are placed in incubators and monitored to prevent them from overheating. Management of this disease gets easier as the patient ages. Adults with HED can control their thermoregulation by staying in cool environments or drinking cold drinks to lower the body temperature. Currently, there are studies that aim to find a cure for this abnormality, e.g. gene replacement therapy in animal models.&amp;lt;ref name= PMID24678015&amp;gt;&amp;lt;pubmed&amp;gt;24678015&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=151004</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=151004"/>
		<updated>2014-10-15T04:34:06Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2014_Group_Project_8&amp;diff=151001</id>
		<title>Talk:2014 Group Project 8</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2014_Group_Project_8&amp;diff=151001"/>
		<updated>2014-10-15T04:33:41Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2014discussionheader}}&lt;br /&gt;
==Peer Reviews==&lt;br /&gt;
===1===&lt;br /&gt;
Let me start by saying that the “Muscle Gains” section is funny but obviously very irrelevant to the project. Looking at the contents of this page, there seem to be a lot of focus on the development and very little on the other sections. The development section is well-researched and great job on the in-text citations! Some parts look a bit bulky though so maybe try to break some of them down into bulletpoints if possible. A timeline of development is also very helpful in this project.&lt;br /&gt;
&lt;br /&gt;
On abnormalities, very concise and detailed. Try to  write about 3-4 abnormalities and find information on how they’re treated or managed presently. As for historic findings, there is a section on the Wikipage that has old books on embryology. It’s under the “Explore” tab and you’ll see “Historic embryo”. Those books have a lot of information regarding that section. Don’t forget to write about current findings as well. Another thing, try to use images since these really help with understanding the content of the page. Overall, a lot of work has to be done before the due date. I do understand why because there are only two people in this group. Goodluck and I wish you the best in finishing this project!&lt;br /&gt;
&lt;br /&gt;
===2===&lt;br /&gt;
&lt;br /&gt;
The key points of musculoskeletal development appear as headings however there is still much that needs to be clearly discussed beneath each of these points. The main headings are good and specific but some are way too specific and should be under much larger headings, for example, 1.2-1.9 could be subheadings that come under the heading ‘System Development’. ‘Background embryonic development’ is useful to understand but perhaps it is better to not have so much detail, or summarise it in a table. The ‘Abnormalities’ heading is done well, with one disease listed (Duchenne Muscular Dystrophy).  It might be better to have more than one abnormality listed and clearly described as well. I particularly like the use of statistics and genetic references. It seems most of the key points relating to system development have been clearly described, but some tidying up in terms of editing needs to be done. &lt;br /&gt;
&lt;br /&gt;
Also, more work needs to be done on historic findings, current research, models and findings.  Once all the research parts are completed, the timeline can be correctly constructed. Also like the idea of putting a timeline and the heading shows that this is intended. More subheadings could be used to make the page look more organised and pleasing to the eye. &lt;br /&gt;
&lt;br /&gt;
There are also no graphs or tables as well as pictures. A table could be used to make the timeline or highlight the differences between the second, third trimesters and neonatal periods of fetal muscular development. Maybe the initial heading of the page should be changed to ‘Muscular Fetal Development’ to indicate that muscular development is actually being covered instead of both muscular and skeletal. There also isn’t much information regarding limb fetal development, so maybe it would be good to go through that on a deeper level. &lt;br /&gt;
&lt;br /&gt;
It could also help to have images loaded onto the page or to draw flow diagrams to assist in the description of how the muscles develop in the fetal period. For example, upload an image showing the difference between slow twitch and fast twitch muscle fibres or draw a flow chart to show better understanding of the molecular and cellular regulation of fetal myogenesis. &lt;br /&gt;
&lt;br /&gt;
References need to be in one larger section at the end under the heading ‘References’, not two and scattered throughout as is seen. The major section of references appears to be referenced correctly and in-cite references are done very well. There are also many references which are good and show that this group has thoroughly researched their topic. &lt;br /&gt;
&lt;br /&gt;
Overall, this group has done very well and just needs to add more information for certain headings, as well as organise the page a bit better in neater headings and subheadings. Pictures should be added, as well as graphs, tables and own student-drawn images.&lt;br /&gt;
&lt;br /&gt;
===3===&lt;br /&gt;
&lt;br /&gt;
There is no introduction that allows the audience an insight to your project page. This is something that needs to be worked on and maybe add some images also. I’m not sure what I think about the “making gains” section, it’s funny however needs a bit of work. However I do see what you are trying to do here, trying to make it more inviting, interesting and alluring the audience and I appreciate that. &lt;br /&gt;
The Muscle development timeline needs some work and progress. I don’t see a timeline, or dot points, maybe work on format here even if it’s in a table format for this section.&lt;br /&gt;
&lt;br /&gt;
Most of the following sections have great amount of detail with a number of in text citations and this is great to see. However I do notice that there is no images what so ever, not sure if you are having trouble finding, or if you have left this until the last thing, try and draw images, or look at a youtube video that sums one section or maybe the entire system. This could help balance the amount of text you have, making the page more interesting, not overwhelming. Also work on making things more concise and simplifying paragraphs. &lt;br /&gt;
&lt;br /&gt;
Third trimester, neonatal and mechanisms are all sections that need more content in there whether it be images or information there is not much attention given to these areas. &lt;br /&gt;
&lt;br /&gt;
Overall this project page has room for improvement by giving certain sections of the page the attention they deserve. Images are imperative in allowing a balance between text and the image itself. It can sometimes be refreshing, and less overwhelming to see an image among paragraphs of content. Also try and look for a youtube video that can help summaries the content on your page. Try and work on time management, or set a group deadline that everyone has to meet so that all the information can be well up before the due date so your group can have time to edit and add images and play around with the page comfortably. &lt;br /&gt;
Goodluck!&lt;br /&gt;
&lt;br /&gt;
===4===&lt;br /&gt;
&lt;br /&gt;
Overall the Group project page seems to be set out quite well with its headings and sub headings.  Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood.  There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided.  The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later. &lt;br /&gt;
&lt;br /&gt;
To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content.  They are also a great way to make the content clearer especially if there are a number of processes involved in the development.  Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.). &lt;br /&gt;
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).&lt;br /&gt;
&lt;br /&gt;
===5===&lt;br /&gt;
Firstly, I thought the “Making Gains” bit was great- and I can guess who came up with that. I know you’ll take it our prior to submission though haha. The structure of your project is quite good, and the subheadings would make it much easier to read- the only thing is you need to add more content! I think because your system encompasses quite a lot, it would be a better idea for you to put as much information as you can into tables and include diagrams- I saw that musculoskeletal development has quite a few visual resources so it you should use them!&lt;br /&gt;
There are some areas where the content is really sparse, yet others where it is extremely heavy. In these areas, you may benefit from putting your information into bullet points so as to alleviate any confusion that may arise and overall enhance the clarity of your work. The references you have done are quite good, but there appears to be some missing.&lt;br /&gt;
&lt;br /&gt;
Overall, I think your project would greatly benefit from the incorporation of images and diagrams. Because you are describing so much, a visual aid will help you immensely and also assist in retaining the attention of the reader throughout the entirety of the piece.  Also, I see that you have deviated from the recommended headings. This may be a good idea to individualise your project- but make sure all topics are covered.  I think it’s a good start considering you only have two team members, and I’m sure you will be able to pull it all together by the time it is due.&lt;br /&gt;
&lt;br /&gt;
===6===&lt;br /&gt;
Musculoskeletal&lt;br /&gt;
There is no introduction that has been added - you should really add one because its great to introduce the readers to what will be in the wiki page. I hope the person incharge of the first two sections of your group will / does have some work to add soon. Hardly any information has been added to the majority of the assignment, and to be honest, this wiki project has had the least amount of work done on it. You need pictures, diagrams, graphs and a LOT more information. You guys are doing a “musculoskeletal” topic, and I can’t find anything on “skeletal” on your page yet. Mark has posted that your page will only be focusing on fetal muscle development - why not change the name of the page from musculoskeletal to muscular only? That will prepare the reader in regards to the topic being addressed. &lt;br /&gt;
As for abnormalities, all the other pages have on average 5 abnormalities being introduced, whereas this page only has 1. Although it is really well worded and introduced, I think you should try to find at least another 2 abnormalities to put into your group project. &lt;br /&gt;
Sections for historic findings, current research, models and findings will need to be added. &lt;br /&gt;
Your page seems to focus only on how the actual muscle fibres develop, but perhaps, you could write about skeletal muscle development contributing to limb development or something to widen your topics? &lt;br /&gt;
Overall, your page needs a lot more work! Hope you can get a lot of work done until the project is due, make sure to add pictures!&lt;br /&gt;
&lt;br /&gt;
===7===&lt;br /&gt;
&lt;br /&gt;
In this project the development section is well-researched however introduction, historical findings, current models and abnormalities still need some work. The development section is very informative with appropriate use of in-text referencing. However, to prevent having bulks of text, you can create diagrams and flow charts or use bullet points. It would also be great if you could provide a timeline under “muscle development general timeline” section. Background embryonic development section is very helpful but we do not need this much information on embryonic period for this project. You can summarise this information in introduction, so that it provides a starting point and fetal development can be further expanded through the project. The rest of the information regarding system development seems to cover the important points; however it still needs work (for e.g. “second trimester muscular development” section is clearly missing some bits).&lt;br /&gt;
&lt;br /&gt;
The abnormality section only includes one abnormality (Duchenne Muscular Dystrophy). This abnormality is well described but it needs to be referenced. An image of the clinical manifestation of the disease can clearly help with understanding. There are lots of other abnormalities that you can include in this section (We learnt from the musculoskeletal development lecture that musculoskeletal conditions form 20% of all abnormalities at birth). You can also refer to “limb development lecture” to find information on musculoskeletal abnormalities.&lt;br /&gt;
&lt;br /&gt;
Finding information on historic findings might be a little challenging. A suggestion I can make is to search for old articles in PubMed (by adjusting the year). These articles can include key historical events. Review articles that summarise historic findings related to musculoskeletal development may also be helpful. You also need to find information on current research.&lt;br /&gt;
&lt;br /&gt;
Finally, you should add an introduction to your project. It seems like you are more focused on muscular development rather than “musculoskeletal” so you can mention that in your introduction. You can also show creativity by drawing your own diagrams, adding images, and tabulating timeline data. You should also fix the references by putting all the references under one subheading in the bottom of the page.&lt;br /&gt;
&lt;br /&gt;
===8===&lt;br /&gt;
I think this page needs a lot of work in improving the overall layout. First, I think the page would benefit from a more formal introduction that introduces the content of the page in a way that is helpful to your audience. The age could also be improved by breaking it up into ‘Development’, ‘Historic Findings’, ‘Current Research Models and Findings’ as well as the Abnormalities section already included to make it flow better.&lt;br /&gt;
&lt;br /&gt;
The text in under the ‘Molecular and Cellular Reputation of Fetal Myogenesis’ is really good but it is appears as a large slab of information that would be better presented with dot points to break it up and images to make it more interesting. The Abnormalities section is well written but is very brief. This section could be improved by including more abnormalities and the appropriate images. &lt;br /&gt;
&lt;br /&gt;
Overall there is a lot of work to be carried out for this page but I understand that this is a smaller group. Perhaps breaking the work up into those smaller headings mentioned will help you split the work evenly. When all the text is uploaded, make sure that there is an effort to include in text citations to support all your information and images to make the page interesting. Try to avoid writing big slabs of information – tabulate or use dot points to break up large portions of text.&lt;br /&gt;
&lt;br /&gt;
===9===&lt;br /&gt;
&lt;br /&gt;
I think the group has found some useful and relevant sources of information however there still needs to be work done in writing up content under some headings. The structure of the wiki page has been laid out and I think the idea of splitting up the developmental process into three trimesters is a good idea to avoid lengthy paragraphs or an overly lengthy timeline that may be difficult to absorb. I would suggest using a table to write up the timeline with a brief description of what exactly the process occurring involves. There are some references that are missing in the tendon development section. &lt;br /&gt;
&lt;br /&gt;
I think the ‘Molecular and Cellular regulation of fetal myogenesis’ section was the most well written section with a thorough description of the process involved. Try to find relevant pictures and diagrams to accompany this text, they will make the explanation much more beneficial and easier to understand. &lt;br /&gt;
&lt;br /&gt;
Overall a good  structure has been laid out for the wiki page but more content still needs to be added.&lt;br /&gt;
&lt;br /&gt;
===10===&lt;br /&gt;
&lt;br /&gt;
I understand that you only have two people in your group so you have made a good start considering this. It does seem a bit unorganized at the moment though. Be aware that mark has set out guidelines that include that include making sure you have an introduction, historic findings and models. These can be found when you click on the student projects at the top of the page. &lt;br /&gt;
&lt;br /&gt;
The information you do have is good but your page isn’t visually entertaining as there are no images. Adding images makes it more interesting and I particularly recommend student images to make it more student-like and in my opinion these will attract attention from the viewer. Obviously the making gains part, while blatantly funny it is quite irrelevant. &lt;br /&gt;
&lt;br /&gt;
Referencing appears to be a bit of an issue at the moment as some parts have been done well with in text citations but you need to make sure all of the text has in text citations. Also it would be a good idea to put all your references down the bottom of the page to make it look more tidy and aesthetically pleasing. &lt;br /&gt;
&lt;br /&gt;
I like how you have split your page into different parts, it would be a good idea if you were to finish off the general timeline at the start as well. Think about tabulating it as this has been done by other projects and it looks really good. I think the fact that you have only two people you have got just about all the information you need there as it is difficult to do as much as the other groups when there is only two of you. So even the abnormalities part it’s good that you have even one to the effort to have it there. &lt;br /&gt;
&lt;br /&gt;
Overall, a very good start from both of you. I think it’s important to make sure that everything mark has mentioned is put into your page at the start even if there isn’t as much information in each as other pages have. Also make sure you include some sort of images because it’s a bit monotonous at the moment. The referencing needs  a bit of tweaking as well. Best of luck with the rest of the assignment.&lt;br /&gt;
&lt;br /&gt;
===11===&lt;br /&gt;
The Making Gains section is quite funny but as you said, this is not Broscience and I’m sure it will be removed for the final submission. Once that is removed, begin the project with an introduction and the developmental general timeline. The main idea of the timeline is present, however when constructing one, use specific weeks within the foetal period and what developmental changes occur in those weeks. The information found under Background Embryonic development may be used to form the introduction, but if you are going to do that do not make the introduction as detailed as this section is, particularly in terms of the transcription factors and signalling molecules, they can be moved and added into the other sections that look at the various musculoskeletal developments individually.&lt;br /&gt;
&lt;br /&gt;
It is evident that there is great understanding of this topic and that it is only a case of further research and addition of those information to complete the sections. Certain sections lack information all together, such as the Third Trimester Muscular development and Recent findings, whereas other sections only contain the research articles and no summaries of them such as Abnormalities. However I understand this is a draft and that all those areas will be addressed adequately, contributing to the final copy. &lt;br /&gt;
&lt;br /&gt;
Only the Background Embryonic development and Molecular and Cellular regulation of foetal myogenesis have in text citations, whereas the other sections that do contain information are not cited. It might become difficult to later find the correct article from which you obtained the information so it is advised to cite the text while adding it. In terms of the citations present, there is no need for a comma between the superscripts and you have also allocated two sections to references, one subsequent to Abnormalities and another at the bottom of the page, it is best to collate all the references in one list at the end of the page. This is also the case for Abnormalities as there are two subheadings for it, merge them into one. &lt;br /&gt;
&lt;br /&gt;
No images, tables, or timelines are added. The information you have now is well written and divided into small paragraphs, which is a good way of presenting the information, however other forms such as images and tables should be used. A timeline should be added under the Muscle development General Timeline subheading, this may be done as a table or a drawing and uploaded as it simplifies the information and breaks the page from continuous writing. &lt;br /&gt;
&lt;br /&gt;
Overall this group project page is great, containing all the headings and articles present. It is only a matter of summarising those articles and adding the information. All the information present thus far is appropriate and emphasises great research skills.&lt;br /&gt;
&lt;br /&gt;
===12===&lt;br /&gt;
&lt;br /&gt;
The project is split up into different sections well but you need to include an introduction to your project. Really good information and references but use bullet points and diagrams to break up the text so that it is easier to read. There is good information on DMD but you could possibly write about another abnormality linked to muscle development.&lt;br /&gt;
&lt;br /&gt;
===13===&lt;br /&gt;
Introduction is missing. Some information about the functions of the systems and topics going to be covered should be included here. The section ‘making gains’ is funny. However, more work has to be done to make it more interesting.&lt;br /&gt;
&lt;br /&gt;
For the timeline, more information is needed. It would be great to include a table here and describe the changes during different stages (microfibers formation…). Table is also useful to explain the second trimester muscular development&lt;br /&gt;
&lt;br /&gt;
The information under background embryonic development can be summarised and put under introduction as this project should be focused on fetal development.&lt;br /&gt;
&lt;br /&gt;
It is great to have molecular and cellular regulation. However, more diagrams are needed here. It would be better if they are stated in several points rather than a big paragraph. Also, more images are needed for other sections, it would be good to draw the picture as well.&lt;br /&gt;
&lt;br /&gt;
For abnormalities, in-text references are needed. Also, some more abnormalities should be included with the use of images to illustrate them.&lt;br /&gt;
&lt;br /&gt;
Overall, there is a pretty good structure of the website. It could be improved by including some current and historic researches on this topic. Also, more images are needed (as there is none now) to make the webpage more interesting and informative. More contents should be included as well.&lt;br /&gt;
&lt;br /&gt;
===14===&lt;br /&gt;
&lt;br /&gt;
A few sentences should be added to your introduction to better introduce what the project page is about and the main objectives or aims. Timeline needs some work, a few ideas could include a bullet point structure or the use of a simple table with images to accompany the overview of musculoskeletal development. The background embryonic development section is particularly useful to giving the project some background information- internal citations are also well presented. Molecular and cellular regulation section could use some images to increase the visual appeal – perhaps from some recent research papers. Tendon development and abnormalities section could also use some more detail and images. Perhaps some hand drawn images would be useful to help describe difficult concepts. References section is well presented and developed- although a few errors need to be fixed with a few references.  &lt;br /&gt;
&lt;br /&gt;
===15===&lt;br /&gt;
&lt;br /&gt;
This project is still in its early days but the layout and plan is very good. With additional information added to the subheadings, it will be a very interesting student wiki page. Reviewing what has already been completed on this page, it is too content heavy. There are a lot of large chunks of text indicating the student has gone to a lot of effort to find complex research papers. This is further supported by the huge amount of references at the end of the page. However as this is to be a student embryology wiki page, it would help if the passages of text were broken up into bullet points and tables. Furthermore there are no images or student drawn diagrams. These would also help convey the main messages of musculoskeletal development. The sections after tendon development are unfinished and very brief. Furthermore the only in text referencing present is in the first two sections. Citations should be carried through the entire page. &lt;br /&gt;
&lt;br /&gt;
The second trimester muscular development section is particularly clear and to the point. However the information present doesn’t stretch much further than what was covered in the lecture material. By adding diagrams of the pharyngeal arch origins and including further research into this section, its quality will be greatly improved.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===16===&lt;br /&gt;
&lt;br /&gt;
The page is disorganised in certain aspects. The first heading is not appropriate and is not teaching at peer level. Timeline is incomplete could have phases (first trimester, second trimester etc.) and key events put into a table and shown. &lt;br /&gt;
&lt;br /&gt;
There’s good information about the muscle development from myofiber to tubules etc. however there is no period of time given to when the event occurs so it can get confusing maybe include the week in the information. Molecular and cellular regulation is well described but some information such as how IFG1 has found to enhance protein synthesis could be put into a different heading specific on research findings.   Tendon development is much clearer and easier to understand as it to the point and tells it as a series of event. Could include when the process ends only has shown that it started in 20th Carnegie stage&lt;br /&gt;
&lt;br /&gt;
Second and Third trimester information is incomplete although the summary in second Trimester heading is easy to understand it can be expanded upon.  Does anything happen to limb buds in fetal stage maybe could include information of muscles in that. The one Abnormality given is relevant and well summarised. It has been defined and shows how common it is which is good to include. There should be more abnormalities added into this section and possibly picture or diagram helping to visualise how it may look. &lt;br /&gt;
&lt;br /&gt;
Referencing is done in the correct format and it’s good everything is shown as a list on the bottom of the page. Overall the page needs improvement there is some evident of research done however there needs to be more headings added such as Historic findings. The recent finding heading could be placed more up on the page, before abnormality heading. Can have the different trimesters as subheading instead of separate headings. Can include a timeline in table format and also some diagrams or pictures of muscle development in head region and tendon development as well as possibly a video. Good background of embryonic development but since embryonic development is not related the project can summarise it a bit more and add more into fetal development of muscles.&lt;br /&gt;
&lt;br /&gt;
===17===&lt;br /&gt;
&lt;br /&gt;
The introduction to your page is extremely funny, but this is completely irrelevant to the project and should be taken out before you submit the assignment. There are long blocks of texts  on the page, with no tables or any pictures sadly. There should be a some images/digarams/videos for each heading. There is a number of good headings, with information within that needs to be further developed. There is great potential for this group project to develop further. &lt;br /&gt;
&lt;br /&gt;
There is a Heading labelled, 'Muscle development general timeline' however, underneath this section, there is only a small paragraph with no timeline whatsoever. If you don't want to have a timeline in this section of your project, then remove the word 'timeline from this heading'. However, I think a timeline would be a great way to show an overview of the key events of the muscoskeletal system. &lt;br /&gt;
&lt;br /&gt;
There is an broad, and long section of information under &amp;quot;background embryonic development&amp;quot;. Just remember that our projects are about fetal development and not the embryonic stage of the system our project is about. The time spent on writing this section could have been spent on working on other parts of the assignment that require greater attention.&lt;br /&gt;
&lt;br /&gt;
Towards the end of the references list, there are references that have not properly been citied. There also exists a format error in your reference list that would need to be fixed before the final group submission.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===18===&lt;br /&gt;
All Text and no images. Not a good look to go through. some formatting of the text would be a good idea to break up the text in addition to adding images.&lt;br /&gt;
&lt;br /&gt;
The referencing is well done for the content at the top of the page. Whoever is doing the tendon section onward needs to take note of this and add all their references in the same style.&lt;br /&gt;
&lt;br /&gt;
The humour section is unnecessary &amp;quot;information&amp;quot; that i doubt needs to be there. definately consider removing.&lt;br /&gt;
&lt;br /&gt;
The information you have here is good. It will require a lot of work to get it to a point that it is well presented. I understand that it will be difficult with only the two of you in the group. Just keep adding a little bit each day to the sections.&lt;br /&gt;
&lt;br /&gt;
==4==&lt;br /&gt;
This page needs a lot of work; there are sections with little to no information, while others have just slabs of text, some of which have no references. Of those that have info presented, the topic is well covered with the large amount of content. You should use some dot points for some areas where you have a lot of info. You also need to use some images!! They will help to alleviate the slabs of content you have and add some colour to the page. Make sure you caption and reference them correctly, and add the correct copyright info. &lt;br /&gt;
&lt;br /&gt;
Overall, there isn’t much I can say except add content, reference is correctly both in text and at the bottom of the page, and images and use some dot points and/or tables; don’t write everything in large slabs of text. Also, maybe get rid of that 'Muscle Gains' section, unless you actually plan to write something relevant in there haha. Otherwise, Good luck!&lt;br /&gt;
&lt;br /&gt;
==5==&lt;br /&gt;
Let me start by saying, for only having two people in the group, well done. The page should have an introduction though, and this is missing. Just by simply summarizing all the information that will be covered in the page and adding it to the introduction, will improve the overall presentation significantly, you may wish to leave this to last, or edit as you go along. &lt;br /&gt;
&lt;br /&gt;
The section “Making gains” is amusing, but inappropriate and should be omitted from the final submission. The timeline for the page I believe should be put into a table to save time and add to the presentation of the page, it can be easily done if you follow the steps outlined in the ‘editing basics’ page &lt;br /&gt;
&lt;br /&gt;
The background information is comprehensive, however, the page is in desperate need of some images as there are just slabs of text. Images will really help break up the contents of the page and make it visually appealing. &lt;br /&gt;
&lt;br /&gt;
The abnormalities section also seems to be coming along quite well. Keep up the good work. &lt;br /&gt;
&lt;br /&gt;
==6==&lt;br /&gt;
&lt;br /&gt;
This is great work so far from a group consisting of only 2 people. Keep up the good work and continue to work hard in finishing this page. Very admirable.&lt;br /&gt;
&lt;br /&gt;
Overall, I would suggest reformatting and adding pictures to enhance the presentation of this page. Consider the use of lists and tables, throughout this wiki.&lt;br /&gt;
&lt;br /&gt;
Instead of the rather hilarious (but rather inappropriate) ‘Making gains’ subheading, I believe an introduction should be added. Remember to clearly indicate the outcomes that the page hopes to achieve.&lt;br /&gt;
&lt;br /&gt;
I also believe that the development/timeline section of this page is informative, with a very good use of headings and sub-headings. There is excellent evidence of significant scientific research and is correctly referenced and cited. However, this section could be further summarised or improved through the use of a table I believe- just a suggestion however. Adding pictures would also add to the overall understanding of this section.&lt;br /&gt;
&lt;br /&gt;
This page has no information for the “recent findings” or “historic findings” section. Remember to include relevant information/pictures and references to these sections.&lt;br /&gt;
&lt;br /&gt;
The abnormalities section is also looking very promising. Include more varying abnormalities. The abnormality included, DMD, is well written and informative. It needs to be correctly referenced however. &lt;br /&gt;
&lt;br /&gt;
==7==&lt;br /&gt;
In this review I hope to highlight the merits of your project and suggest some areas for improvement in line with the marking criteria. &lt;br /&gt;
&lt;br /&gt;
I see that you have conducted a great amount of research on the fetal development of the musculoskeletal system. The content clearly goes beyond the material covered in the lectures. It was interesting to read about the different transcriptions factors involved in induction and regulation of myoblast differentiation. I think it will be good to see a summary of all this information in a timeline format. I suggest simply highlighting the main developments at each stage. &lt;br /&gt;
&lt;br /&gt;
You have made a good start on abnormalities. I suggest that you begin by selecting one abnormality include Description; Epidemiology; Cause and Treatment. You can add more later.&lt;br /&gt;
&lt;br /&gt;
The page needs a little more structure. Make sure you include appropriate sub-heading and organise the information before you submit the project. Remember we were asked specifically to address the topics of current research and historic findings. &lt;br /&gt;
&lt;br /&gt;
Finally it would be good see some images to support the text. Perhaps diagrams on tendon development would help summarise the process. &lt;br /&gt;
&lt;br /&gt;
Great work so far!! Hope this feed back helps. &lt;br /&gt;
&lt;br /&gt;
==8==&lt;br /&gt;
&lt;br /&gt;
Overall, the project has some very detailed sections and some sections where content is scarce. It would be helpful to start off with an introduction of the musculoskeletal system so the reader is aware of its components and what the page intends to cover. The timeline of muscle development has good potential, I understand it is still being planned at this stage and with further research, it could definitely be effective. A table format would be useful to present this information. The following sections on background embryonic development and fetal myogenesis are well-researched and have a lot of content, however I would consider breaking it down into dot points to improve readability. The sections are cited correctly in-text though, which is good to see.&lt;br /&gt;
&lt;br /&gt;
There is much more improvement in the tendon and second trimester development sections, as the chunks of text have been reduced to provide a succinct summary, however these need to have citations also. The use of some images here, either hand-drawn or from online would be beneficial, to have a balance between text and pictures and make the page more visually appealing. Other than the abnormalities section which provides a good, concise summary of Duchenne Muscular Dystrophy, the following sections seem to be only references at this stage. As long as these are used to compose some relevant paragraphs/dot points, this is fine considering there is still time to improve the page. &lt;br /&gt;
&lt;br /&gt;
Overall, this page has good potential as the groundwork has been completed; it is now more a matter of writing up more information, adding images and possibly a relevant video. The part on ‘making gains’ would need to be removed for the final, but otherwise, it is definitely a decent amount of work so far, especially considering the few group members involved.&lt;br /&gt;
&lt;br /&gt;
==9==&lt;br /&gt;
&lt;br /&gt;
“Making Gains” is pretty funny but offcourse irrelevant to this project.&lt;br /&gt;
Your timeline needs a lot of work done as it is missing copious amounts of information.&lt;br /&gt;
Background embryonic development section is well detailed though it lacks images to aid the information. Also molecular and cellular regulation of fetal myogenesis section is the same; it is well informed but lacks images.&lt;br /&gt;
Much more is needed on tendon development, second and third trimester muscular development, neonatal, mechanisms/structure of muscle fibres and abnormalities.&lt;br /&gt;
Over all very good in text citations for the development (top) section. References from the background section should be at the bottom of the page with other references. The page mostly looks like a bulk of writing so include images where possible. A LOT more work is needed but I understand your situation as your group only has 2 members now so do as much as you can and GOOD LUCK!&lt;br /&gt;
&lt;br /&gt;
------&lt;br /&gt;
&lt;br /&gt;
==10==&lt;br /&gt;
&lt;br /&gt;
The project doesn’t have an introduction yet; however information such as what the Musculoskeletal system is about, the features of the system as well as the difference between the embryonic and fetal stages of development should be mentioned. Not to mention a brief summary of each key subheading such as abnormalities under introduction e.g. any deformations in the fetal stages of musculoskeletal development can result in to such and such abnormalities which will be addressed. This will help the viewer’s understand what the project will be going through. I like the ‘making gains’ subheading as it adds humour to the page and engages the viewers. The general timeline needs information including what events take place at certain phases of fetal development. This could be present in a table to make the information more clear. It’s good that the project has information on the embryonic development so that the viewers can understand how the fetus arises to that point in development (fetal period). &lt;br /&gt;
&lt;br /&gt;
All of the content seems to relate to the key topic and is appropriately paragraphed. However much of the content is still missing such as in ‘recent findings’ and ‘introduction’. More information could be added under the associated ‘trimesters’ and ‘abnormalities’. There are no historic findings which is great to have on your page for viewer’s fascination into the group project. Members could search on pubmed about the musculoskeletal system and view dates on the side that may contain key findings for historical events. Also a glossary list should be added to help viewers understand the content more instead of just being confused at some sections.&lt;br /&gt;
&lt;br /&gt;
There are no images on this page and definitely needs to be added with the appropriate information such as the description, referencing, copyright issues and ‘student template’. If images are not readily available, it is best to draw them. Also captions should be added on the page to state what the images are showing. As for referencing, there are  some sections which shows incite referencing such as in the content under ‘Molecular and Cellular regulation of fetal myogenesis’ and some that don’t have any like in ‘tendon development’. There needs to be references in all sections. There is a huge list of references under ‘abnormalities’ which need to be placed all under one ‘references subheading’; similarly to any other reference list on the page. Number 15 of the reference list has an error in it and needs to be fixed right away. Overall, this is a working progress and if the group makes edits based on the peer-reviews received, this could enhance their project.&lt;br /&gt;
&lt;br /&gt;
=Discussion=&lt;br /&gt;
&lt;br /&gt;
Week 5 &lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 22:34, 26 August 2014 (EST)&lt;br /&gt;
Hi guys &lt;br /&gt;
After discussing in lab last week we tried to divide the categories and work as following; &lt;br /&gt;
* skeletal and cartilaginous development - Joel&lt;br /&gt;
* muscular development - Gowtem&lt;br /&gt;
* overall skeletal and muscular arrangement macroscopically - Danny &lt;br /&gt;
What do you guys think about addressing these topics as well &lt;br /&gt;
* Historical findings&lt;br /&gt;
* Abnormalities &lt;br /&gt;
* New findings&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 12:44, 27 August 2014 (EST)&lt;br /&gt;
Great idea m8 Danny can probably also do abnormalities, remember to post any articles of particular relevance to New/historical findings. To complete after main content assembled&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 01:02, 28 August 2014 (EST)&lt;br /&gt;
I would suggest that we narrow down the topic to focusing on the appendicular musculoskeletal system, so that;&lt;br /&gt;
*To make work load more managable&lt;br /&gt;
*To avoid the multiple highly specialised and irregular muscles/bones of the head&lt;br /&gt;
*The muscles I would suggest to include in are all muscles which have attachments to the appendicular skeleton including axioappendicular muscles (petoralis major, pectoralis minor, subclavious, serratus anterior, Latissimus Dorsi, Traps, levator scap, rhomboid major and minor.&lt;br /&gt;
*Joints and tendons are included in the musculoskeletal system, we should about wether we want to have a section for them.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 09:05, 31 August 2014 (EST)&lt;br /&gt;
&lt;br /&gt;
Hi guys just posted the topics of abnormalities of muscle and skeletal system im gonna talk bout and references of relevant articles to the topics. Sorry for being late btw&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 14:57, 9 September 2014 (EST)&lt;br /&gt;
Disregard the rest of the stuff I said in earlier discussions, I believe that to make it significantly easier we just do muscular system. I will Reformat everything to make it make sense.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 01:51, 10 September 2014 (EST) &lt;br /&gt;
Yeah completely agree, I think focusing on the muscular system would be much easier than doing both. Appendicular muscles sounds good - so muscles of limbs. Could divide it into upper and lower limbs. May have to talk about bone/cartilage a bit to describe how the muscle forms around it. Maybe how developing of muscles in embryonic development is important and eventually affects origin and insertions and actions of muscles when fully developed.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 12:56, 17 September 2014 (EST) This link shows a very good description of myogenesis; http://books.google.com.au/books?id=1ZRCMRXbbwoC&amp;amp;pg=PA38&amp;amp;lpg=PA38&amp;amp;dq=primary+secondary+myofibers&amp;amp;source=bl&amp;amp;ots=RSRcVVe5xr&amp;amp;sig=eDJBF_3qkYzA8WSin1tnbzT2xYY&amp;amp;hl=en&amp;amp;sa=X&amp;amp;ei=OegYVL_UHpOB8gWMxoDYAw&amp;amp;ved=0CCoQ6AEwAw#v=onepage&amp;amp;q&amp;amp;f=false&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 12:27, 20 September 2014 (EST)&lt;br /&gt;
Ill add a bit more on embryonic muscle development guys&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 22:30, 6 October 2014 (EST)&lt;br /&gt;
Here are some article which would probably be helpful&lt;br /&gt;
Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo: Nrk2b and NAD+ in muscle morphogenesis&lt;br /&gt;
Coexpression of two distinct muscle acetylcholine receptor a-subunits during development&lt;br /&gt;
&lt;br /&gt;
At the moment I have a general structure for tendon development and abnormalities will add to wiki tommorrow.&lt;br /&gt;
&lt;br /&gt;
the good indepth morphogenesis studies focus on gluteus maxximus, extrenal urethra spincter, tensor veli palatini very little are done of the other muscles, so will try to apply the conclusions from these studies to related skeltal muscles&lt;br /&gt;
&lt;br /&gt;
--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 12:11, 15 October 2014 (EST) Will add Fetal akinesia deformation sequence (FADS) to abnomralities and amyoplasia&lt;br /&gt;
&lt;br /&gt;
----[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 12:58, 15 October 2014 (EST)&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/14383771&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/17340805&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/13218323&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=150989</id>
		<title>User:Z3417796</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3417796&amp;diff=150989"/>
		<updated>2014-10-15T04:20:39Z</updated>

		<summary type="html">&lt;p&gt;Z3417796: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{StudentPage2014}}&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
===Lab 1===&lt;br /&gt;
[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:52, 6 August 2014 (EST)&lt;br /&gt;
===Lab 2===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:54, 13 August 2014 (EST)&lt;br /&gt;
===Lab 3===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:41, 20 August 2014 (EST)&lt;br /&gt;
===Lab 5===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:54, 3 September 2014 (EST)&lt;br /&gt;
===Lab 6===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:21, 10 September 2014 (EST)&lt;br /&gt;
===Lab 7===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:12, 17 September 2014 (EST)&lt;br /&gt;
===Lab 8===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 11:16, 24 September 2014 (EST)&lt;br /&gt;
===Lab 9===&lt;br /&gt;
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:20, 8 October 2014 (EST)&lt;br /&gt;
==Practice==&lt;br /&gt;
===Links===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed]&lt;br /&gt;
===Reference===&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25084016&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25084016]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;25084016&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
==Belbin Model Team Roles==&lt;br /&gt;
Although I feel as if aspects of my personality and demeanour may fall into more than one specific category, the Monitor Evaluator may be the role that best describes my contribution to group work tasks :) &lt;br /&gt;
===Monitor Evaluator===&lt;br /&gt;
Monitor Evaluators are fair and logical observers and judges of what is going on in the team. Since they are good at detaching themselves from bias, they are often the ones to see all available options with the greatest clarity and impartiality. They take a broad view when problem-solving, and by moving slowly and analytically, will almost always come to the right decision. However, they can become very critical, damping enthusiasm for anything without logical grounds, and they have a hard time inspiring themselves or others to be passionate about their work.&lt;br /&gt;
==Individual Assessments==&lt;br /&gt;
===Lab 1: Fertilisation Reference===&lt;br /&gt;
====Reference 1====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/23835722&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23835722]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;23835722&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
The usefulness of low O2 concentrations in human IVF technology is an ongoing question with numerous laboratories still uncertain as to the actual influence and significance on clinical outcome. The purpose of this randomised clinical trial was to investigate the impact of atmospheric vs. low concentrations of oxygen (O2) during the complete process of human zygote and embryonic development.  The study was performed utilising sibling oocytes with the differentiations between the two O2 culture levels measured from fertilisation, from embryo until blastocyst formation, through pregnancy and live birth. &lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 258 women who underwent intracytoplasmic sperm injection (ICSI) treatment with a minimum of eight oocytes extracted. The recovered oocytes were cultured and randomly allocated into one of two-treatment groups- incubation in either 5% or 20% O2 conditions. The temperature in both incubators was 37 °C. Evaluation of embryonic development was made in terms of fertilisation, cleavage and the quality of both the embryo and blastocyst. Secondary factors assessed included implantation, maintenance of pregnancy and live births.&lt;br /&gt;
====Results====&lt;br /&gt;
A sum of 3,638 matured (metaphase II phase) oocytes were extracted through the study, of which 1833 were incubated under 5% O2 conditions and 1805 sibling oocytes under the alternate 20% O2 treatment condition. Levels of fertilisation and rates of cleavage between the two treatment groups showed no significant differences. However, significant distinctions were seen with the 5% O2 group, which presented significantly more blastomeres (p&amp;lt;0.05), a greater quantity of high quality day 3 embryos (p&amp;lt;0.02) in addition to a significantly increased number of available embryos, per cycle, for transfer and freezing (31.6% vs. 23.1% for the 20% O2 group; P&amp;lt;0.0001). The lower oxygen concentration also seemed to suggest a better influence on clinical outcomes, with significantly higher rates of implantation, pregnancy and live births (22.1% vs. 10.3%, P&amp;lt;0.03; 38.2% vs.18.4%, P&amp;lt;0.05, 34.2% vs. 15.8%, P&amp;lt;0.05 respectively).&lt;br /&gt;
====Reference 2====&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/25071849&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/25071849]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC4111889&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====Purpose====&lt;br /&gt;
Developments in human embryo culturing and cryoconservation techniques in IVF technology have lead to a modification in embryo transfer procedures from early fresh or frozen-thawed cleavage embryo to fresh or frozen-thawed blastocyst stage transfer. The purpose of the clinical trial was to investigate the impact of fresh or frozen-thawed embryo and blastocyst stage transfer upon clinical outcome.&lt;br /&gt;
====Method====&lt;br /&gt;
The participants of the study comprised of 1150 women who underwent IVF treatment cycles or intracytoplasmic sperm injection (ICSI) treatment with a total number of 1891 oocytes extracted. The total number of recovered oocytes were experimentally divided into one of two transfer groups- fresh embryonic (n=1150) and frozen-thawed embryonic (n=741) transfers. The 1150 women of the fresh embryonic transfer group were further sub-composed of either cleavage stage (n=799, &amp;lt;35 years old and n=194, &amp;gt;35 years old) or blastocyst stage (n=131, &amp;lt;35 years old and n=26, &amp;gt; 35 years old). The 741 women of the frozen-thawed embryonic transfer group were further sub-composed of either cleavage stage (n=159, &amp;lt;35 years old and n=53, &amp;gt;35 years old) or cleavage stage extended blastocyst culture (n=111, &amp;lt;35 years old and n=26, &amp;gt;35 years old) or blastocyst stage transfer (n=276, &amp;lt;35 years old and n=52, &amp;gt;35 years old). Statistical analysis was then applied to all collected data.&lt;br /&gt;
====Results====&lt;br /&gt;
Data on the rates of clinical pregnancy in the fresh cleavage stage embryo and fresh blastocyst transfer in women &amp;lt;35 years were statistically significant (52.7% and 35.88%),(p&amp;lt;0.0001). A statistically significant difference was also noted for the same treatment groups in women &amp;gt;35 years of age (41.24% vs. 26.92%). Rates of clinical pregnancy in the frozen-thawed cleavage stage embryo and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (35.29% and 59.8%) and in women &amp;gt;35 years of age (11.32% and 55.8%). Rates of clinical pregnancy between the post thaw cleavage stage extended blastocyst and frozen-thawed blastocyst transfers were also significant (p&amp;lt;0.0001) in women &amp;lt;35 years (47.75% vs. 59.8%) and women &amp;gt;35 years (46.15% vs. 55.8%). The rates of clinical pregnancy differ considerably between the fresh cleavage stage embryo transfers and frozen-thawed cleavage stage embryo transfers in women &amp;lt;35 years of age (52.7% vs. 35.29%) and (41.24% vs. 11.32%) in women &amp;gt;35 years of age. No statistical significant difference was recorded for rates of multiple pregnancy, abortion and ectopic pregnancy between any of the treatment groups. Rates of clinical pregnancy in the frozen-thawed blastocyst transfer group showed the most pleasing clinical outcome among the fresh and frozen embryo transfers.&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] These are good summaries of the 2 articles. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 2: Uploading a Research Image===&lt;br /&gt;
[[File:Normal Human 2-cell Embryo.jpeg|right|300px]]&lt;br /&gt;
Image of a normal human 2-cell embryo with two equal blastomeres (B), a single polar body formation (PB) enclosed by an intact zona pellucida (ZP)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2898034&amp;lt;/pubmed&amp;gt;| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898034/?report=classic]&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] This is a relevant image, you have misidentified the species as &amp;quot;human&amp;quot; when this is &amp;quot;mouse&amp;quot;, also in the file name. (4/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 3: Researching your Project Sub-Heading===&lt;br /&gt;
====Timeline====&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12807866&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12807866&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID12860885&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;12860885&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID14506305&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14506305&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID20712587&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;20712587&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID22679138&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22679138&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID21367775&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21367775&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Current Research====&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID25015802&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;25015802&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24910745&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24910745&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24520485&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24520485&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID24855117&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24855117&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23723064&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt; 23723064&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] You have included many relevant references related to your project sub-headings. (5/5)&lt;br /&gt;
&lt;br /&gt;
===Lab 4===&lt;br /&gt;
====1) '''Human umbilical cord blood-derived mesencyhmal stem cell transplantation for the treatment of spinal cord injury'''====&lt;br /&gt;
&lt;br /&gt;
The objectives of the study were to investigate the effects of human umbilical cord blood-derived mesencyhmal stem cell (HUCB-MSC) transplantation in the functional repair of spinal cord injury (SCI). The study utilised 46 adult Wistar rats, which were randomly allocated into three treatment groups: Injury (n=15), control (n=15) and transplantation (n=16). Rats in the control group received a physiological saline injection into the site of injury whereas those in the transplantation group received HUCB-MSC suspension into the site of injury.&lt;br /&gt;
Parameters examined after treatment were behaviour, using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale in weeks one, two and four and histological changes measured through immunohistochemistry (IHC) procedures performed on samples from the rats sacrificed four weeks after subsequent treatment. Analysis of results showed that two weeks following treatment the BBB assessment of the rats in the transplantation group were significantly greater than that of the injury and control groups (P&amp;lt;0.05). Even greater recovery was apparent four weeks following treatment in the transplantation group with the BBB assessment once again, showing statistically significant results (P&amp;lt;0.05) when compared with the other treatment groups. The rats in this group have the ability to stand on their hind limbs and demonstrated coordinated fore and hind limb movements. The expression of Neuron Specific Enolase (NSE) and Glial fibrillary acidic protein (GFAP) in spinal cord tissue was detected via IHC measurements. No levels of these nerve repair factors were detected in the injury or control groups in week four, however a low level of NSE+ cells and a high- level of GFAP+ cells was measured in the transplantation group. The processes of the GFAP+ grew in length and a number of the cells were fibrous and dendritic-cell like, becoming entwined into a neural network within the spinal cord. Therefore the study has shown that following the transplantation of HUCB-MSC’s into the injury site of a rat spinal cord, these implanted cells were able to adapt and differentiate into functioning nerve cells, which was involved in the recovery and regeneration of the damaged spinal cord.&lt;br /&gt;
&lt;br /&gt;
http://www.ncbi.nlm.nih.gov/pubmed/24940417&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/24940417]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;24940417&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
====2) Vascular shunts in the fetal circulation====&lt;br /&gt;
&lt;br /&gt;
During fetal development the liver and lungs are non-functional, thus a series of shunts exist in the fetal circulation so that these organs are by-passed.&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 1: Ductus Arteriosus'''= Connects the pulmonary artery to the proximal descending aorta to shunt most of the blood away from the lungs&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 2: Ductus Venosus'''= Shunts a portion of the left umbilical vein blood flow directly to the inferior vena cava&lt;br /&gt;
&lt;br /&gt;
- '''Shunt 3: Foramen Ovale'''= Shunts highly oxygenated blood from right atrium to left atrium. Located in atrial septum.&lt;br /&gt;
===Lab 5===&lt;br /&gt;
====1)====&lt;br /&gt;
Bronchopulmonary Dysplasia: CAUSES&lt;br /&gt;
Bronchopulmonary dysplasia is a chronic lung condition most prevalent among&lt;br /&gt;
premature infants requiring oxygen and mechanical ventilation. In most cases infants who develop BPD are greater than 10 weeks premature, weigh less than 1kg and often have severe breathing difficulties, often being born with serious respiratory distress syndrome (RDS). The lungs of a premature infant are delicate and normally not fully developed and as a result can be acutely injured by such factors as mechanical ventilation and oxygen therapy, which may cause irritation and inflammation of an infant’s lung. The acute damage may then result in the interference or inhibition of lung alveolar and vascular development. Certain factors can cause irritation or damage to premature infants lungs: (Alan H. Jobe 2001). &lt;br /&gt;
* Ventilation machines use pressure to force air into the airway and lungs of newborns with breathing problems or those who cannot breathe on their own. The pressure of the ventilators may however lead to irritation and harm to the babies’ lungs and is therefore only used when crucial&lt;br /&gt;
*High levels of oxygen administered though oxygen therapy can inflame the lining of the lungs and injure the airways- may also lead to slow lung development in premature infants&lt;br /&gt;
* Infections may lead to inflammation of delicate lung tissue and subsequent narrowing of airways. Troublesome breathing often results which may also increase the need for ventilation and oxygen support measures&lt;br /&gt;
* A number of studies demonstrate a possible link between genetics and the acquisition of BPD (NHLBI, 2014).&lt;br /&gt;
References:&lt;br /&gt;
*What Causes Bronchopulmonary Dysplasia? - NHLBI, 2014. What Causes Bronchopulmonary Dysplasia? - NHLBI, NIH. [ONLINE] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/bpd/causes.html. [Accessed 10.9.14]&lt;br /&gt;
*Alan H. Jobe and Eduardo Bancalari &amp;quot;Bronchopulmonary Dysplasia&amp;quot;, American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 7 (2001), pp. 1723-1729.&lt;br /&gt;
===Lab 7===&lt;br /&gt;
&amp;lt;ref name=&amp;quot;PMID23882220&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;23882220&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
* Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical:&lt;br /&gt;
The pancreas and other gastrointestinal organs are embryologically derived from endodermal origins. The pancreas is developed via the union of two separate buds; the dorsal and the ventral, which appear at the foregut/midgut junction by the fifth week of gestation. The dorsal pancreatic bud forms initially and will produce a segment of the head and uncinate process whole body and tail of the pancreas whereas the ventral bud surfacing alongside the bile duct will form only a small segment of the head and uncinate process. Subsequent expansion and rotation of the duodenum eventually unites both dorsal and ventral buds forming the complete pancreas. The pancreatic duct will form via the fusion of the ventral bud duct and distal part of the dorsal bud duct- this will provide fro the exocrine function. Endocrine function however is provided via the endodermal cell differentiation into islet cells. Whilst the exocrine function of the fetus will initiate postnatally, endocrine function- secretion of insulin, glucagon and somatostatin can be measured from 10 to 15 weeks onwards. The purpose of the study was to investigate the impact of maternal nutrition upon the intrauterine environment, more specifically the key stages of human pancreatic development and factors controlling  β-cell development and mass. Little is known about the key molecular pathways and mechanisms that control the adaptive programming of β-cells however it is understood that maternal factors including over nutrition or obesity may affect the ability to maintain fetal β-cell mass resulting in a heightened risk of type 2 diabetes in adulthood.&lt;br /&gt;
&lt;br /&gt;
*Identify the embryonic layers and tissues that contribute to the developing teeth:&lt;br /&gt;
'''Odontoblast:''' Cells of neural crest origin, that is part of the outer surface of the dental pulp and functions in dentiogenesis.&lt;br /&gt;
&lt;br /&gt;
'''Ameloblast:''' Cells derived from oral epithelium tissue of ectodermal origin annd function in the deposition of tooth enamel.&lt;br /&gt;
&lt;br /&gt;
'''Periodontal ligament:''' Develops from the dental sac of the tooth germ and function as a type of specialised connective tissue fiber that attaches a tooth to the alveolar bone.&lt;br /&gt;
&lt;br /&gt;
===Lab 8===&lt;br /&gt;
'''Embryonic Development of the Human Ovary:'''&lt;br /&gt;
&lt;br /&gt;
The chromosomal sex of the human embryo is resolute from the stage of oocyte fertilisation by the type of sperm- either X or Y carrying that fertilises the X-bearing oocyte. The early stages of genital development (&amp;lt;7weeks) in both male and female are similar and thus collectively referred to as the ‘indifferent stage’ of sexual development. The sources of embryonic gonad development are the mesothelium lining the posterior abdominal wall, underlying mesenchyme and primordial germ cells. The earliest phases of gonad development occur within the 5th week of gestation, as there is a thickening of the mesothelium on the medial side of the mesonephros, which is the primitive kidney. Propagation of this epithelium and the underlying mesenchyme will produce the gonadal ridge. By week 6, gonadal cords will then develop and grow into the underlying mesenchyme. The indifferent gonad now comprises an external cortex and internal medulla. The cortex region will now differentiate into an ovary in those embryos with an XX sex chromosome with the medulla region degenerating. Additionally in week 6, there are two pairs of genital ducts that are present- the mesonephric ducts (wolffian ducts) and the paramesonephric ducts (mullerian ducts), which have a leading role in the development of the female reproductive system.  The mesonephric ducts of female embryos will degenerate due to the lack of testosterone. The paramesonephric ducts will develop majority of the female genital tract. The uterine tubes will form from the unfused cranial portion of the duct, whereas the caudal portions develop into the uterovaginal primordium, which will produce the uterus and superior part of the vagina. Gonadal development is a gradual process in the female embryo and by week 10 onwards there is further gonad and external genital growth. The cortical cords ranging from the surface epithelium of the maturing ovary into the underlying mesenchyme grow in size and primordial germ cells are integrated into them. By 16 weeks of development the cords will start to breakdown into isolated cell clusters known as primordial follicles. Each primordial follicle will enclose an oogonium, which originated from a primordial germ cell. A single layer of flattened follicular cells, which are derived from the surface epithelium, surrounds the oogonium. Many oogonia will degenerate before birth with approximately 2 million that will remain and grow to become primary oocytes. &lt;br /&gt;
&lt;br /&gt;
===References===&lt;br /&gt;
&amp;lt;pubmed&amp;gt; 24741072&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
Moore, K.L. &amp;amp; Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders&lt;br /&gt;
&lt;br /&gt;
[[File:Bailey328.jpg|right|300px]] &lt;br /&gt;
'''Image Reference:''' Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co.&lt;br /&gt;
&lt;br /&gt;
===Peer Review of Student Projects===&lt;br /&gt;
====Project 1====&lt;br /&gt;
Introduction part is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity.  Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺&lt;br /&gt;
====Project 2====&lt;br /&gt;
The introduction section of the page is well written and provides a nice overview to the whole project that unifies each subheading of the project as a whole. Some potential ideas for historic findings section may be to use some sort of timeline or table with some visual effects through historical images/ drawings. Developmental timeline is clear and concise however this section would be more effective with a greater amount of detail and perhaps a panel of images to convey visually each stage of development. The current research models section was very well written with two relevant current papers discussed- perhaps a few additional papers can be cited- even under an expanded box format so that the readers can be linked to other current studies in the area of interest. The explanation of the figure is also really well presented and described. The section with the subheadings of kidney, ureter and bladder is very well researched and presented- well informed, great use of images and also well referenced. One area for improvement could perhaps be presenting the information in a simpler way as at times it seems too bunched up- maybe smaller bullet points.  The image within the urethra subheading is missing a figure caption. Abnormalities section was very descriptive and informative- may be a few more abnormalities could be listed. Overall reference section is also done correctly although some sections individual references need to be integrated into this overall section. &lt;br /&gt;
====Project 3====&lt;br /&gt;
A nice overview is presented for basic information to be presented onto the project page, with a descriptive introduction into the topic of GIT. Perhaps this section could include a brief mention of the aims of the page and perhaps a few images to make it more visually appealing. Timeline section is particularly extensive, however perhaps the layout can be altered- either adding further information to each developmental stage or even using a table format with images to aid the readers understanding of the processes. The subheadings of this section were also a particularly nice way to structure the information. Recent findings needs a bit more work- perhaps a particular focus could be established for this section of even links to a few articles organised by research into particular organs of the GIT. A few images would also increase the visual appeal to this section. The main body of information (foregut, midgut and hind-gut) are well covered and written- there is evidence of extensive research and work put into this section. The hand drawing idea was also particularly a good idea also with a proper description added to the image. Formatting to this section could be a little more unified however as some section use different styles of bullet points and ways to present the information. Deformities section is greatly informative; perhaps a few more should be presented with accompanying images. The overall references section was formatted correctly. &lt;br /&gt;
====Project 4====&lt;br /&gt;
This page overall looks really fantastic and highly informative! A brief introduction is lacking at the start of the page- would be nice to briefly introduce the topic of the page and the intended goals for the page to achieve to present to the reader. This section would also nicely unify the contents of the project as a whole. The system development part has very extensive information with a great use of formatting styles- with the use of bullet points and the table format. Perhaps the placement of the image and video could be re-integrated into this section as it seems fairly isolated and doesn’t unify this section greatly. Also a brief description could be added to the image and video to describe what is being presented. The video however is a great idea and a good choice of one too! Very informative and simplifies the information being presented. Current research section looks great so far; few changes to formatting would be beneficial (i.e. with font styles and the general structure of bullet points can be made more visually presentable). There is evidence of extensive research however and the use of subheadings also nicely structures this section. There is an error with one of the uploaded images, which should be corrected however. The information presented within the historic findings section seems highly extensive, although perhaps the formatting could be altered to make it look less bulky and easier to read and understand for the reader. The abnormalities section is greatly done, very informative and looks fantastic, well done! All references should be integrated into the final references section that is already been established. &lt;br /&gt;
====Project 6====&lt;br /&gt;
An introduction section should be added to the beginning of this page as it is highly useful to unify the project as a whole and so as to introduce the topics to be discussed to the reader. A basic overview of what particular endocrine organs are to be presented as well as associated abnormalities may need to be mentioned briefly. The individual subheadings focusing on a particular endocrine organ is a nice layout, which is then further, subdivided into the timeline, abnormalities and recent findings sections. This is a well thought out layout and seems to work well however there is a lack of unison between different sections and this chosen layout- perhaps more communication is needed between team members. The structure of the timeline is also particularly well done in these sections and nicely introduces each organs developmental stages. The use of extensive images is also great to see, the brief description of each image/ figure is also highly relevant. Perhaps a few hand drawn images can also be added- as this would be beneficial for student learning as it is simple and easier way to present a process of development. The written information is nicely presented also, there doesn't seem to be too much muddled information, it is concise and informative. Historic findings section doesn't seem to have been completed so perhaps could be integrated into each individual subheading or an overall small section briefly touching on this topic also. So overall I believe the cohesiveness and flow of the project seems to lacking, however there is evidence of extensive research and development of ideas very clearly. The references of each section also need to be unified under a single subheading at the end of the project.&lt;br /&gt;
====Project 7====&lt;br /&gt;
At this stage this project seems to be put together very well. The introduction has a very neat layout and structure, it is well developed and integrates the concepts of the whole page together well. Fetal development section has a fantastic diagram, very relevant and has a great visual appeal and is very helpful form of understanding the concepts being presented. The bullet points are a nice way to break up the page so that it doesn’t appear too clumped, however it may be useful to at times have a little more detail – particularly in the fetal development section. The brain development section has nice formatting with the use of bullet points and then a table. Perhaps at times small paragraphs can also be useful especially when explaining complex processes like the developing brain. The images are well described in this section too. Perhaps another improvement can be the addition of hand drawn images as this is a student page and a simplistic drawing of complex concepts can make things easier to understand for the reader. The current research models section seems to be extensively researched, however shouldn’t be left as it is at them moment- the referencing should be worked on and integrated into the final section of references. Some images may also be of benefit to this section. Abnormalities section is great so far! The final reference section has a good start- although more of the references must be integrated into this section. &lt;br /&gt;
====Project 8====&lt;/div&gt;</summary>
		<author><name>Z3417796</name></author>
	</entry>
</feed>