Embryology - User contributions [en-gb]

User:Z3333429

2014-10-29T00:07:19Z

Z3333429: /* Lab Attendance */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)

Lab 11: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:51, 22 October 2014 (EST)

Lab 12: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:06, 29 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Lab Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

==Lab 11 Assessment==
'''Efficient Generation of Myelinating Oligodendrocytes from Primary Progressive Multiple Sclerosis Patients by Induced Pluripotent Stem Cell'''<ref name="PMID25254339"><pubmed>25254339</pubmed></ref>

This study attempted to develop an affective and efficient method of deriving oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). There is hope that this method will pave the way for treatment of progressive Multiple Sclerosis (MS) using neuroprotective and remyelinating techniques. Adherent cultures of Human Embryonic Stem Cells (hESC) and Induced Pluripotent Stem Cells (hiPSC) were induced to neural differentiation using dual SMAD and treated with retinoids from the onset of differentiation, produced an increase in OLIG2 progenitors and oligodendrocyte progenitor cell (OPC) yields. The strategies used in this study were also able to produce oligodendrocytes differentiation from neural iPSCs at significantly faster rate than previous studies had demonstrated.

The study also revealed that he methods used were capable of producing iPSCs from progressive MS patients that were viral and integration free and that differentiates efficiently into oligodendrocytes. These OPCs were shown to be fully functional and free of abnormalities when incorporated into mouse models where OPCs differentiated into mature oligodendrocytes and remyelinate axons. These findings in particular demonstrate a proof of concept for transplantation of iPSC derived neural cells into patients for the development of future cell-replacement therapies. This technology may also provide a valuable insight into the disease pathogenesis of neurodegenerative diseases and offer the platform to study drug treatments for diseases such as MS and Amyotrophic Lateral Sclerosis in the hope that they can produce attenuated rates of decline in these patients. There is a need for future studies that compare the potential differences between iPSCs derived from patients suffering from MS and from healthy controls.

'''Reference'''
<references/>

User:Z3333429

2014-10-28T23:37:19Z

Z3333429: /* Lab Assessment 10 */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)

Lab 11: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:51, 22 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Lab Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

==Lab 11 Assessment==
'''Efficient Generation of Myelinating Oligodendrocytes from Primary Progressive Multiple Sclerosis Patients by Induced Pluripotent Stem Cell'''<ref name="PMID25254339"><pubmed>25254339</pubmed></ref>

This study attempted to develop an affective and efficient method of deriving oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). There is hope that this method will pave the way for treatment of progressive Multiple Sclerosis (MS) using neuroprotective and remyelinating techniques. Adherent cultures of Human Embryonic Stem Cells (hESC) and Induced Pluripotent Stem Cells (hiPSC) were induced to neural differentiation using dual SMAD and treated with retinoids from the onset of differentiation, produced an increase in OLIG2 progenitors and oligodendrocyte progenitor cell (OPC) yields. The strategies used in this study were also able to produce oligodendrocytes differentiation from neural iPSCs at significantly faster rate than previous studies had demonstrated.

The study also revealed that he methods used were capable of producing iPSCs from progressive MS patients that were viral and integration free and that differentiates efficiently into oligodendrocytes. These OPCs were shown to be fully functional and free of abnormalities when incorporated into mouse models where OPCs differentiated into mature oligodendrocytes and remyelinate axons. These findings in particular demonstrate a proof of concept for transplantation of iPSC derived neural cells into patients for the development of future cell-replacement therapies. This technology may also provide a valuable insight into the disease pathogenesis of neurodegenerative diseases and offer the platform to study drug treatments for diseases such as MS and Amyotrophic Lateral Sclerosis in the hope that they can produce attenuated rates of decline in these patients. There is a need for future studies that compare the potential differences between iPSCs derived from patients suffering from MS and from healthy controls.

'''Reference'''
<references/>

2014 Group Project 1

2014-10-24T07:05:48Z

Z3333429: /* Abnormalities */

{{ANAT2341Project2014header}}

=Respiratory =
[[File:3D model of the air way tree.jpg|centre|800px]]
This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system, the lung. It places particular emphasis on the overview of fetal respiratory development. Discussion of current and historic findings during the fetal development of the respiratory system will also be elaborated on. Unfortunately, during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this, there will be a detailed explanation of abnormalities that we find relevant to this system to conclude.

==Development of the Respiratory system Overview==

Current knowledge of the development of the respiratory system portrays how understanding has advanced over time, from what was historically known about the system until what is known today. The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. [[File:Respiratorysystem2.png|thumb|550px|'''Embryonic Origins of Respiratory System.''']] The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Historic findings==

Historic knowledge of the shifts in understanding of the respiratory development during the fetal stage is essential for robust appreciation of current accepted ideas of how this system comes to be in the human body. Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since before 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px|Historic image of the human embryo]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|200px|thumb|William Harvey (1578-1657)]]William Harvey discovered that the lungs were not the organ responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs, which was later discovered to be what we know today as surfactant, was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Hummer et al discovered that there occurred a reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth. This experiment was initially performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Current Understandings and Areas of Research==

The development of the respiratory system is one of the most crucial for the survival of the neonate, and hence it is a system that is highly studied. Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation

'''a) Domain branching''': In this type of mode, the respiratory network develops and continues to grow in a direction perpendicular to the future trachea. New lung bud formations become apparent appear on either side of the stalk. The most recent lung buds that are formed are shown in lighter colors, typically where outgrowths are observed.

'''b) Planar bifurcation:''' these types of bifurcations form the thin edges of the lobes

'''c)Orthogonal bifurcation:''' this type of bifurcation creates the lobe surfaces and fill the interior part of the respiratory system with the diaphragm, lies beneath.

Note both b) and c)as the name suggests, these branching models are responsible for bifurcating the airways in consecutive rounds of tubular divisions

'''d) Trifucation''': Researches have recently identified that this mode of branching is responsible for the backbone of the respiratory tree<ref><pubmed>22844507</pubmed></ref>

|}

{|
|-bgcolor="E0 FF FF"
|

[[File:Lung Fgf10 expression cartoon.jpg|left|300px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]
• Another recent study conducted in 2013 <ref><pubmed>24004663</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

|}

{|
|-bgcolor="CEDFF2"
|

• [[File:Signalling factors in lung branching cartoon.png|right|400px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]
A research group in 2011, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH) <ref><pubmed>22359491</pubmed></ref><ref>,<pubmed>24004663</pubmed></ref>. Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.
From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

[[File:Figure5-1.jpg|left|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

A Comparison of lung development stages in the human and rabbit with their relationship towards gestational length
can be found in Figure 1 of this article
[http://www.formatex.org/microscopy3/pdf/pp417-425.pdf]

==Abnormalities==

As mentioned earlier, the development of the respiratory system in the fetus is one that has been known for many years dating back into history, and one that is still currently studied today. However, despite knowledge of respiratory system development being well understood, unfortunately, there still occurs a myriad of abnormalities in the neonate due to complications in development during the fetal stages of the developing human. In this section, we will discuss some of the primary abnormalities that is found in respect to the development of the respiratory system in the fetus.

===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

==References==
<references/>

2014 Group Project 1

2014-10-24T06:23:52Z

Z3333429:

{{ANAT2341Project2014header}}

=Respiratory =
[[File:3D model of the air way tree.jpg|centre|800px]]
This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system, the lung. It places particular emphasis on the overview of fetal respiratory development. Discussion of current and historic findings during the fetal development of the respiratory system will also be elaborated on. Unfortunately, during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this, there will be a detailed explanation of abnormalities that we find relevant to this system to conclude.

==Development of the Respiratory system Overview==

Current knowledge of the development of the respiratory system portrays how understanding has advanced over time, from what was historically known about the system until what is known today. The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. [[File:Respiratorysystem2.png|thumb|550px|'''Embryonic Origins of Respiratory System.''']] The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Historic findings==

Historic knowledge of the shifts in understanding of the respiratory development during the fetal stage is essential for robust appreciation of current accepted ideas of how this system comes to be in the human body. Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since before 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px|Historic image of the human embryo]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|200px|thumb|William Harvey (1578-1657)]]William Harvey discovered that the lungs were not the organ responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs, which was later discovered to be what we know today as surfactant, was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Hummer et al discovered that there occurred a reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth. This experiment was initially performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Current Understandings and Areas of Research==

The development of the respiratory system is one of the most crucial for the survival of the neonate, and hence it is a system that is highly studied. Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation

'''a) Domain branching''': In this type of mode, the respiratory network develops and continues to grow in a direction perpendicular to the future trachea. New lung bud formations become apparent appear on either side of the stalk. The most recent lung buds that are formed are shown in lighter colors, typically where outgrowths are observed.

'''b) Planar bifurcation:''' these types of bifurcations form the thin edges of the lobes

'''c)Orthogonal bifurcation:''' this type of bifurcation creates the lobe surfaces and fill the interior part of the respiratory system with the diaphragm, lies beneath.

Note both b) and c)as the name suggests, these branching models are responsible for bifurcating the airways in consecutive rounds of tubular divisions

'''d) Trifucation''': Researches have recently identified that this mode of branching is responsible for the backbone of the respiratory tree<ref><pubmed>22844507</pubmed></ref>

|}

{|
|-bgcolor="E0 FF FF"
|

• [[File:Lung Fgf10 expression cartoon.jpg|right|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]
Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH) <ref><pubmed>22359491</pubmed></ref><ref>,<pubmed>24004663</pubmed></ref>. Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

[[File:Figure5-1.jpg|left|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

A Comparison of lung development stages in the human and rabbit with their relationship towards gestational length
can be found in Figure 1 of this article
[http://www.formatex.org/microscopy3/pdf/pp417-425.pdf]

==Abnormalities==

As mentioned earlier, the development of the respiratory system in the fetus is one that has been known for many years dating back into history, and one that is still currently studied today. However, despite knowledge of respiratory system development being well understood, unfortunately, there still occurs a myriad of abnormalities in the neonate due to complications in development during the fetal stages of the developing human. In this section, we will discuss some of the primary abnormalities that is found in respect to the development of the respiratory system in the fetus.

===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

==References==
<references/>

2014 Group Project 1

2014-10-24T06:06:28Z

Z3333429: /* Respiratory */

{{ANAT2341Project2014header}}

=Respiratory =
[[File:3D model of the air way tree.jpg|centre|800px]]
This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system, the lung. It places particular emphasis on the historic understandings of the respiratory system followed by an overview of fetal respiratory development. Discussion of current and historic findings during the fetal development of the respiratory system will also be elaborated on. Unfortunately, during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this, there will be a detailed explanation of abnormalities that we find relevant to this system to conclude.

==Historic findings==

Historic knowledge of the shifts in understanding of the respiratory development during the fetal stage is essential for robust appreciation of current accepted ideas of how this system comes to be in the human body. Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since before 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px|Historic image of the human embryo]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|200px|thumb|William Harvey (1578-1657)]]William Harvey discovered that the lungs were not the organ responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs, which was later discovered to be what we know today as surfactant, was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Hummer et al discovered that there occurred a reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth. This experiment was initially performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Development of the Respiratory system Overview==

Current knowledge of the development of the respiratory system portrays how understanding has advanced over time, from what was historically known about the system until what is known today. The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. [[File:Respiratorysystem2.png|thumb|550px|'''Embryonic Origins of Respiratory System.''']] The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Understandings and Areas of Research==

The development of the respiratory system is one of the most crucial for the survival of the neonate, and hence it is a system that is highly studied. Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation

'''a) Domain branching''': In this type of mode, the respiratory network develops and continues to grow in a direction perpendicular to the future trachea. New lung bud formations become apparent appear on either side of the stalk. The most recent lung buds that are formed are shown in lighter colors, typically where outgrowths are observed.

'''b) Planar bifurcation:''' these types of bifurcations form the thin edges of the lobes

'''c)Orthogonal bifurcation:''' this type of bifurcation creates the lobe surfaces and fill the interior part of the respiratory system with the diaphragm, lies beneath.

Note both b) and c)as the name suggests, these branching models are responsible for bifurcating the airways in consecutive rounds of tubular divisions

'''d) Trifucation''': Researches have recently identified that this mode of branching is responsible for the backbone of the respiratory tree<ref><pubmed>22844507</pubmed></ref>

|}

{|
|-bgcolor="E0 FF FF"
|

• [[File:Lung Fgf10 expression cartoon.jpg|right|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]
Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH) <ref><pubmed>22359491</pubmed></ref><ref>,<pubmed>24004663</pubmed></ref>. Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development [[File:Figure5-1.jpg|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

A Comparison of lung development stages in the human and rabbit with their relationship towards gestational length
can be found in Figure 1 of this article
[http://www.formatex.org/microscopy3/pdf/pp417-425.pdf]

==Abnormalities==

As mentioned earlier, the development of the respiratory system in the fetus is one that has been known for many years dating back into history, and one that is still currently studied today. However, despite knowledge of respiratory system development being well understood, unfortunately, there still occurs a myriad of abnormalities in the neonate due to complications in development during the fetal stages of the developing human. In this section, we will discuss some of the primary abnormalities that is found in respect to the development of the respiratory system in the fetus.

===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

==References==
<references/>

2014 Group Project 1

2014-10-24T05:32:55Z

Z3333429: /* 1. The Conducting system - The respiratory network */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Development of the Respiratory system Overview==

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. [[File:Respiratorysystem2.png|thumb|550px|'''Embryonic Origins of Respiratory System.''']] The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Understandings and Areas of Research==

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation

'''a) Domain branching''': In this type of mode, the respiratory network develops and continues to grow in a direction perpendicular to the future trachea. New lung bud formations become apparent appear on either side of the stalk. The most recent lung buds that are formed are shown in lighter colors, typically where outgrowths are observed.

'''b) Planar bifurcation:''' these types of bifurcations form the thin edges of the lobes

'''c)Orthogonal bifurcation:''' this type of bifurcation creates the lobe surfaces and fill the interior part of the respiratory system with the diaphragm, lies beneath.

Note both b) and c)as the name suggests, these branching models are responsible for bifurcating the airways in consecutive rounds of tubular divisions

'''d) Trifucation''': Researches have recently identified that this mode of branching is responsible for the backbone of the respiratory tree<ref><pubmed>22844507</pubmed></ref>

|}

{|
|-bgcolor="E0 FF FF"
|

• [[File:Lung Fgf10 expression cartoon.jpg|right|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]
Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH) <ref><pubmed>22359491</pubmed></ref><ref>,<pubmed>24004663</pubmed></ref>. Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development [[File:Figure5-1.jpg|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T05:30:22Z

Z3333429: /* 1. The Conducting system - The respiratory network */

2014 Group Project 1

2014-10-24T05:22:36Z

Z3333429: /* Abnormalities */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Development of the Respiratory system Overview==

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. [[File:Respiratorysystem2.png|thumb|550px|'''Embryonic Origins of Respiratory System.''']] The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Understandings and Areas of Research==

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation

'''a) Domain branching''': In this type of mode, the respiratory network develops and continues to grow in a direction perpendicular to the future trachea. New lung bud formations become apparent appear on either side of the stalk. The most recent lung buds that are formed are shown in lighter colors, typically where outgrowths are observed.

'''b) Planar bifurcation:''' these types of bifurcations form the thin edges of the lobes

'''c)Orthogonal bifurcation:''' this type of bifurcation creates the lobe surfaces and fill the interior part of the respiratory system with the diaphragm, lies beneath.

Note both b) and c)as the name suggests, these branching models are responsible for bifurcating the airways in consecutive rounds of tubular divisions

'''d) Trifucation''': Researches have recently identified that this mode of branching is responsible for the backbone of the respiratory tree<ref><pubmed>22844507</pubmed></ref>

|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH) <ref><pubmed>22359491</pubmed></ref><ref>,<pubmed>24004663</pubmed></ref>. Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development [[File:Figure5-1.jpg|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T04:07:44Z

Z3333429: /* Development of the Respiratory system Overview */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Development of the Respiratory system Overview==

[[File:Respiratorysystem2.png|thumb|'''Embryonic Origins of Respiratory System.''']] The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Understandings and Areas of Research==

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development [[File:Figure5-1.jpg|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T04:00:54Z

Z3333429: /* Development of the Respiratory system Overview */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

==Development of the Respiratory system Overview==

[[File:Respiratorysystem2.png|thumb|'''Embryonic Origins of Respiratory System.''']]The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Understandings and Areas of Research==

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

==1. '''The Conducting system''' - The respiratory network==

{|
|-bgcolor="lavenderblush"
|

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

==2. '''The Functional Unit'''-Alveolus==

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

• This article <ref><pubmed>24429276</pubmed></ref> looks at the current findings of different physiological factors that affect normal neonatal, functioning lungs upon during fetal development. The size of the paired organ to be able to exchange carbon dioxide with oxygen for the very first time at birth, is crucial to be able to withstand that pressure. As we know surfactant, is a lipid-protein composite that aids in this process. Both these epithelial cells that lines this tract a play important role and crucial to the function of the lung prior to birth and especially post-natally (Type 2alveolar cells) because <ref><pubmed>24058167</pubmed></ref>:

::::::A) Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

::::::B) Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

However, current research suggests that the production of surfactant which is reliant on hormonal factors, have little influence on fetal lung growth. In contrast, the following physiological lung growth factors were found to permit the lungs to express their inherent growth potential.

==Current Models==

When considering models of research for analysing human development, animals such as the zebrafish, rabbit and mouse are most popular. These models have been used as part of research for scientists to study how different animals can be used to mimics the way the lung is developed in humans. These models have been chosen for various reasons, their genomic patterns, however, are the main reason. For example, at around E16.5 in the mouse, lung development switches from branching morphogenesis to the canalicular and saccular stages <ref><pubmed>18654673</pubmed></ref> . These, in turn, lead to the final process of alveologenesis that generates the functional units for gas exchange. The timing of alveolar development varies between species. In mice it occurs postnatally (∼P5–30), but in humans few alveoli have formed before birth and the process continues for many months- years afterwards.

[[File:Mouse.jpg|300px|right|thumb|The mouse-The most popular used animal model in today's research]]

The reason why these animal models are currently used in research is for a number of reasons. Below is a list of reasons why the mouse model is widely used as part of research within the scientific community:

::• The mouse reproduces quickly (in 21 days) <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Mouse generate many offspring. Anywhere between 8-20 at one time easily <ref>https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development</ref>
::• Have similar genomic patterns which can be used as model to explain human embryonic and fetal development [[File:Figure5-1.jpg|thumb| A complete diploid set of metaphase chromosomes from the laboratory mouse (Mus musculus) is shown.]]
::• Ethical considerations <ref>http://www.oneofus.eu/wp-content/uploads/2014/06/One-of-Us.pdf</ref>
::• Cost effective

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

File:Respiratorysystem2.png

2014-10-24T03:49:59Z

Z3333429: ==Lower Respiratory Tract== A drawing depicting basic features of the human lower respiratory tract including the thyroid cartilage, rib cage and diaphragm. To reveal the internal structures of the left lung, the skeletal structures and heart have been...

==Lower Respiratory Tract==
A drawing depicting basic features of the human lower respiratory tract including the thyroid cartilage, rib cage and diaphragm. To reveal the internal structures of the left lung, the skeletal structures and heart have been removed and the left lung has been sectioned in the coronal plane.

===Reference===
'''Bibliography'''
Netter, F. (2011). ''Atlas of human anatomy.'' Philadelphia, PA: Saunders/Elsevier.

Beginning six months after publication, I, z3333429 grant the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.

{{Template:Student Image}}

2014 Group Project 1

2014-10-24T02:42:26Z

Z3333429:

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

• It was previously thought alveolar type I arise from type II cells but recent studies propose otherwise. By using molecular markers on the mouse model, this research <ref><pubmed>24499815</pubmed></ref> concludes that during development Type I and II cells arise directly from a bipotent progenitor, whereas after birth new Type I derive from rare, self-renewing, long-lived, mature Type II cells that produce slowly expanding clonal foci of alveolar renewal. Mapping alveolar cell locations is important for cancer treatment for patients.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300x230px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300x230px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T02:34:08Z

Z3333429:

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic findings
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|[[File:William Harvey.jpg|400px|thumb|"William Harvey"]]William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named '''alveolar differentiation'''. There are two types of epithelial cells that typically line this tract and both play important role. These two types are described below and provide important background information for the modern research today.

• Two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

• Although the first breath the newborn takes is after existing the birth canal, a recent article suggests that the two types of alveolar cells only appear to be mature 1 day prior to birth, when the distal tube dilates. <ref><pubmed>24499815</pubmed></ref>. This is a major concern for preterm infants, who many not have complete developed airways by the time that the new infant is born. This can lead to serious diseases including Idiopathic Pulmonary Fibrosis and Respiratory Distress Syndrome (For more information about this visit Newborn Respiratory Distress Syndrome under the "Abnormalities" section of this page)

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|framed|right|300px|'''Postmortem revealing congenital laryngeal atresia.''']]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|framed|right|300px|'''Laryngeal atresia caused by Congenital High Airway Obstruction with hyperechoic lungs.''']]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs, subglottic stenosis, inversion of the diaphragm and hyperechoism of the lungs<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T02:23:17Z

Z3333429: /* Congenital High Airway Obstruction Syndrome (CHAOS) */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Year
!align="center" valign="center"|Historic finding
|-
|align="center" valign="center"|400-300BC
|align="center" valign="center"|Hippocrates acknowledged the role of spine deformities in leading to dysfunctional lung development and respiration. This deformity was later identified as scoliosis. <ref name="PMID5118050"><pubmed>5118050</pubmed></ref>
|-
|align="center" valign="center"|1628
|align="center" valign="center"|William Harvey discovered that the lungs were not responsible for blood flow throughout the body, contrary to popular belief at the time. <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|1661
|align="center" valign="center"|[[File:Lung_historical_image.PNG|400px|thumb|"Historical image of lung development"]]Marcello Malpighi was an Italian scientist who contributed greatly to medicine, particularly the understanding of anatomy. He was a pioneer biologist to utilise newly invented microscopes to closely observe the human body. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli of the lung. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref> <ref name="PMID1399659"><pubmed>1399659</pubmed></ref>
|-
|align="center" valign="center"|Early 1900s
|align="center" valign="center"|Studies specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>
|-
|align="center" valign="center"|1902
|align="center" valign="center"|J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>
|-
|align="center" valign="center"|1929
|align="center" valign="center"|The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.
|-
|align="center" valign="center"|1954
|align="center" valign="center"|Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.
|-
|align="center" valign="center"|1959
|align="center" valign="center"|The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.
|-
|align="center" valign="center"|1963
|align="center" valign="center"|Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|align="center" valign="center"|1994
|align="center" valign="center"|Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>
|-
|}
|}

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
[[File:LaryngealAtresia.jpg|right|300px|Postmortem revealing congenital laryngeal atresia]]Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|right|300px]]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
[[File:CHAOS.jpeg|right|300px|Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome]]Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T02:16:55Z

Z3333429: /* Congenital High Airway Obstruction Syndrome (CHAOS) */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|right|300px]]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
[[File:CHAOS.jpeg|right|300px|Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome]]Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

2014 Group Project 1

2014-10-24T02:13:28Z

Z3333429: /* Congenital High Airway Obstruction Syndrome (CHAOS) */

{{ANAT2341Project2014header}}

=Respiratory =

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
[[File:Oral cavity.png|thumb|right|550px|'''The development of the larynx from the 4th and 6th pharyngeal arches''']]
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Expression of Tbx4 and Tbx5 in the developing lung and trachea''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS [[File:4 subdivisons.jpg|thumb|right|550px|'''The four significant divisions in the respiratory system and the change in epithelium within their regions. ''']]

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|
{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|'''Image of newly formed lung bud''']] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}

[[File:Lung development overiview.png|thumb|center|550px|'''An overview of the development of the respiratory system from the embryonic to fetal stage''']]

==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
[[File:CHAOS.jpeg|right|300px]]Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

File:CHAOS.jpeg

2014-10-23T22:34:43Z

Z3333429: /* Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome */

==Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome==
An image showing the affects of Congenital High Airway Obstruction Syndrome (CHAOS) discovered during postmortem of a fetus. The white arrow indicates tracheal atresia and hyperechoism of the lungs can be seen.

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). ''Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature.'' Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

File:LaryngealAtresia.jpg

2014-10-23T22:33:53Z

Z3333429: /* Laryngeal Atresia */

==Laryngeal Atresia==
Postmortem revealing congenital laryngeal atresia (arrow) and hyperechoic lungs.

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). ''Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature''. Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

File:LaryngealAtresia.jpg

2014-10-23T22:31:29Z

Z3333429: /* Reference */

==Laryngeal Atresia==
Postmortem revealing congenital laryngeal atresia (arrow).

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). ''Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature''. Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

File:LaryngealAtresia.jpg

2014-10-23T22:31:09Z

Z3333429: ==Laryngeal Atresia== Postmortem revealing congenital laryngeal atresia (arrow). ===Reference=== Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Tw...

==Laryngeal Atresia==
Postmortem revealing congenital laryngeal atresia (arrow).

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature. Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

File:CHAOS.jpeg

2014-10-23T22:30:53Z

Z3333429: /* Reference */

==Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome==
An image showing the affects of Congenital High Airway Obstruction Syndrome (CHAOS) discovered during postmortem of a fetus. The white arrow indicates tracheal atresia.

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). ''Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature.'' Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

File:CHAOS.jpeg

2014-10-23T22:27:53Z

Z3333429: ==Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome== An image showing the affects of Congenital High Airway Obstruction Syndrome (CHAOS) discovered during postmortem of a fetus. The white arrow indicates tracheal atresia. ===Ref...

==Laryngeal Atresia caused by Congenital High Airway Obstruction Syndrome==
An image showing the affects of Congenital High Airway Obstruction Syndrome (CHAOS) discovered during postmortem of a fetus. The white arrow indicates tracheal atresia.

===Reference===
Artunc Ulkumen, B., Pala, H., Nese, N., Tarhan, S. and Baytur, Y. (2013). Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature. Case reports in obstetrics and gynecology, 2013.

===Copyright===
Copyright © 2013 Burcu Artunc Ulkumen et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

2014 Group Project 1

2014-10-23T21:06:39Z

Z3333429: /* Meconium Aspiration Syndrome (MAS) */

{{ANAT2341Project2014header}}

=Respiratory =

==Introduction==

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY

The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Tbx4 and Tbx5 are expressed around the condensing cartilage mesenchyme and in the intercartilage mesenchyme.''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|

{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|Image of newly formed lung bud]] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}
==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency - caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

File:CPAM.jpg

2014-10-23T20:44:07Z

Z3333429: ==Tomographic Image showing Congenital Pulmonary Airway Malformation== Tomographic image of chest showing abscess in the right pulmonary lobe as a result of Congenital Pulmonary Airway Malformation. ==Reference== <pubmed>17555585</pubmed> [http://www...

==Tomographic Image showing Congenital Pulmonary Airway Malformation==

Tomographic image of chest showing abscess in the right pulmonary lobe as a result of Congenital Pulmonary Airway Malformation.

==Reference==
<pubmed>17555585</pubmed>
[http://www.ncbi.nlm.nih.gov/pubmed/17555585| Pulmonary congenital cystic adenomatoid malformation, type I, presenting as a single cyst of the middle lobe in an adult: case report.]

==Copyright==
Copyright © 2007 Morelli et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

{{Template:Student Image}}

2014 Group Project 1

2014-10-23T20:19:41Z

Z3333429: /* References */

{{ANAT2341Project2014header}}

=Respiratory =

==Introduction==

This page focuses on the development of the respiratory system during the fetal stage, exploring the two significant zones and the major organ of the respiratory system,the lung. This page emphasis further on the lung development, current and historic findings during the fetal development of the respiratory system.
Unfortunately during the fetal development of the respiratory system, some things may go wrong leading to abnormalities in this important system. In respect to this there will be great mention of some abnormalities in detail.

=== Overview===

The respiratory system consists of organs and tissues that assist in breathing. Lungs are the most important organ for respiration. Humans have two lungs, a left and a right lung both located in the chest covered by many tissue, muscles and bones to protect them. The purpose of respiratory system is for gas exchange to occur, gas exchange is the removal of carbon dioxide and intake of oxygen into the lungs. Gas exchange is imperative for the function of life as oxygen is needed to working muscles.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

The respiratory system starts developing at week 4 of the embryo and a great deal of the development continues to take place in the fetal stage. A substantial portion of the respiratory system is formed by germ layer endoderm. The lung buds are lined by epithelium derived from the endodermal layer which later on differentiates into the respiratory epithelium. Nerves and neural innervations of the lungs are derived from ectoderm, on the other hand splanchnic mesoderm contributes to the pulmonary blood vessels, smooth muscle,cartilage and connective tissue.

This system has many airways that allows the movement of air from nose or mouth to the lungs. Some of the airways include;
*Nose (including the nasal cavity)
*Mouth
*Larynx
*Trachea
*Bronchi and their branches

During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that until about week 37 or birth . However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus is in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and are filled up with air automatically. The lungs do not inflate completely until about 2 weeks of the new born. The surfactant in each alveoli assists in keeping the lungs open and prevents them from collapsing.<ref>Cite this page: (2014) National Heart, Lung, and Blood Institute Health. Retrieved 20 September, 2014, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/</ref>

The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

=== Development of the Conducting Zone===

The conducting zone is made up nose to bronchioles, the main function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and are where nasal cavities are lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY

The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm-lined depression and separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx which then forms the vestibule of oral cavity. <ref name="PMH11936451 "><pubmed>11936451</pubmed></ref>

LARYNX

The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle as well as the laryngeal cartilages, and they develop from the 4th to the 6th pharyngeal arch mesenchyme. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>
[[File:Embryonic Trachea.png|thumb|right|550px|'''Tbx4 and Tbx5 are expressed around the condensing cartilage mesenchyme and in the intercartilage mesenchyme.''']]

TRACHEA

The laryngotracheal tube develops in the 4th week. The oseophagotracheal ridge separating the diverticulum forms the trachea.The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea. The trachea then divides into 2 bonchial buds, giving rise to the main bronchi, left main and right main.<ref name="PMH11992723 "><pubmed>11992723</pubmed></ref>

BRONCHI

The bronchi is formed in week 4 and the lung buds develop and further divide into more divisions making up 2 divisions for the left and the 3 for the right. These secondary bronchi (3 branches on the right and 2 on the left), then again divided into tertiary bronchi which occurs in week 7. The surrounding mesenchyme then develop into bronchopulmonary segments.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

BRONCHIOLES

By the 24th week there would have formed approximately 17 subdivisions. After the birth of the baby the bronchiole tree further divides another 6 more divisions.<ref name="PMH12107102 "><pubmed>12107102</pubmed></ref>

=== Development of the Respiratory Zone===
[[File:Respriatory zone.png|thumb|right|550px|'''Visualise airways.''']]
The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli.The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>

TERMINAL BRONCHIOLES

Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.They are lined with simple columnar epithelium. This first begins to develop between week 12 and 13 of the fetus. They develop from thin squamous epithelium, and then differentiate into alveolar cells type 1 and alveolar cells type 2.<ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLAR DUCTS

The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. Alveolar ducts begin to develop during the late fetal period until about 8 years postnatally. They develop with extremely thin walls with many capillaries that are in close association with the alveolar epithelial cells. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>

ALVEOLI

The alveoli is where the carbon dioxide and the oxygen exchange. Each alveolar consists of alveolar cells; type 1 and type 2. Type 1 is a membranous pneumocyte and it serves for gas exchange, on the other hand type 2 is a granular pneumocyte that produces surfactant and it reduces surface tension and prevents the alveoli from collapsing. There would be a remodelling of the alveolar wall that results in a single capillary network, that concludes in the maturation however not a full-sized lung. <ref name="PMH8815817 "><pubmed>8815817</pubmed></ref>

===Lung Development Stages===

{|
|-bgcolor="CEDFF2"
|

{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"| [[File:Lung bud.png|thumb|right|Image of newly formed lung bud]] Lung buds would have formed as well as the lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Lung buds are lined by endodermal derived epithelium that differentiates into respiratory epithelium, these line the airways and specialised epithelium like the on on the alveoli.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include, the formation of extensive airway branching of about 14 or more generations of branching, resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. <ref>Cite this page: Mazurová, Y. Hrebíková, H. Embryology: Respiratory System. Retrieved 26 September, 2014, from http://web.lfhk.cuni.cz/histologie/Histols_web/Vyuka/en/tuition/general/doc/histology_II/G_II_lect_11_E_respir_syst.pdf </ref>The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref> The differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.<ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. <ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood. <ref name="PMH20692626 "><pubmed>20692626</pubmed></ref>
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar.<ref>Cite this page: Rothstein, P (2014) Lung Development. Retrieved September 10, 2014, from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development
</ref>Postnatally from 1-3 years the alveoli will continue to form and in as a result increases the surface area for gas exchange. <ref name="PMH24058167 "><pubmed>24058167</pubmed></ref>
|-
|}
|}
==Current Research and Direction of Future Areas of Investigation==

<iframe width="420" height="315" src="//www.youtube.com/embed/iktuxwfGpWE" frameborder="0" allowfullscreen></iframe>

Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:

# The '''Conducting system'''- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The '''Functional unit'''- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see table above for more information about the properties of each stage of lung development). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

{|
|-bgcolor="lavenderblush"
|

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch<ref><pubmed>24004663</pubmed></ref>:

:::a) Domain branching [[File:Four Models of Lung Branching.jpg|600px|thumb|Modes of branching: (a) lateral branching, (b) planar bifurcation,
(c) orthogonal bifurcation and (d ) trifurcation]]
:::b) Planar bifurcation
:::c) Orthogonal bifurcation
:::d) Trifucation
|}

{|
|-bgcolor="E0 FF FF"
|

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|275px|thumb|The three types of spatial distributions of FGF10 expression generate different branching modes: (c) elongation, (d ) terminal bifurcation and (e) lateral budding. This picture depicts a model used in modern research, outlining the development of the conducting system of the lung]]

|}

{|
|-bgcolor="CEDFF2"
|

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.[[File:Signalling factors in lung branching cartoon.png|right|425px|thumb|FGF10 is transcribed at high levels in the distal mesenchyme (grey) and experiments suggest that FGF10 promotes both the proliferation of the endoderm and its outward movement (green arrow). FGF10 stimulates the expression of SHH in the epithelium (red). SHH reversibly binds its receptor Ptc1 which is expressed in the mesenchyme (grey). SHH-Ptc binding results in the repression of FGF10 expression]]

From their research they also conclude that the sequence of branching events may be the result of different growth speeds:

::::::::::::::Faster growth factors---> triggers lateral branching

::::::::::::::Slow growth factors----> bifurcated branching

|}

2. '''The Functional Unit'''-Alveolus

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

==Current Models==

==Animal Models==

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency -caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

==References==
<references/>

==Glossary==
'''occlusion'''Blockage or obstruction of a vessel

File:Respiratorysystem1.jpeg

2014-10-23T20:14:55Z

Z3333429: /* Reference */

==Basic Drawing of Adult Respiratory System==
A drawing depicting basic features of the adult human respiratory system from the trachea to the bronchioles and also including the rib cage and diaphragm. To reveal the internal structures of the left lung, the skeletal structures and heart have been removed and the lung has been drawn as a coronal section.

===Reference===
'''Bibliography'''
Netter, F. (2011). ''Atlas of human anatomy.'' Philadelphia, PA: Saunders/Elsevier.

Beginning six months after publication, I, z3333429 grant the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.

{{Template:Student Image}}

File:Respiratorysystem1.jpeg

2014-10-23T20:09:14Z

Z3333429: ==Basic Drawing of Adult Respiratory System== A drawing depicting basic features of the adult human respiratory system from the trachea to the bronchioles and also including the rib cage and diaphragm. To reveal the internal structures of the left lung...

==Basic Drawing of Adult Respiratory System==
A drawing depicting basic features of the adult human respiratory system from the trachea to the bronchioles and also including the rib cage and diaphragm. To reveal the internal structures of the left lung, the skeletal structures and heart have been removed and the lung has been drawn as a coronal section.

===Reference===
<ref>Netter, F. (2011). Atlas of human anatomy. Philadelphia, PA: Saunders/Elsevier.</ref>

Beginning six months after publication, I, z3333429 grant the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.

{{Template:Student Image}}

2014 Group Project 1

2014-10-22T02:06:27Z

Z3333429:

{{ANAT2341Project2014header}}

=Respiratory =

==Introduction==

The respiratory system allows the body to take in oxygen and exhale carbon dioxide. The respiratory system is formed by the endoderm. The splanchnic mesoderm develops into connective tissue, cartilage and muscle of the respiratory system. The respiratory system moves the air in from the nose to the pharynx, larynx, trachea, bronchus and alveoli, which is where gas exchange occurs. During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that till about week 37 or birth is the fetal stage. However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus are in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and fill up with air automatically. The lungs do not inflate completely till about 2 weeks of the new born. The surfactant in each alveoli helps keep the lungs open and prevents it from collapsing.
The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

===Conducting Zone===

The conducting zone is made up nose to bronchioles and its function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and is where nasal cavity is lined with cilia, mucous membrane and consists of blood filled capillaries.

ORAL CAVITY
The oral cavity is formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm lined depression, separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx forms the vestibule of oral cavity.

LARYNX
The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle.

TRACHEA
The epithelial cells from the foregut endoderm invade the surrounding mesenchyme to form the trachea.
[[File:Embryonic Trachea.png|thumb|right|'''Tbx4 and Tbx5 are expressed around the condensing cartilage mesenchyme and in the intercartilage mesenchyme.''']]

BRONCHI
The bronchi is formed in week 4 and the lung buds develop and further divide each into more divisions. The left 2 and the right 3.

BRONCHIOLES
These bronchioles will continue to divide until 17 subdivisions. After the baby is born the the bronchiole tree further divides 6 more divisions.

===Respiratory Zone===

The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli. The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli.

TERMINAL BRONCHIOLES
Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs.

ALVEOLAR DUCTS
The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream.

ALVEOLI
The alveoli is where the carbon dioxide and the oxygen exchange.

==Lung Development Stages==

{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"|Lung buds would have formed and lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx. Lung buds are lined by endodermally derived epithelium which differentiates into respiratory epithelium that lines the airways and specialized epithelium that lines the alveoli. [[File:Lung bud.png|thumb|right|Image of newly formed lung bud]]
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include the formation of extensive airway branching of about 14 or more generations of branching resulting in terminal bronchioles. Endodermal lung buds undergo branching only if they are exposed to bronchial mesoderm.The conducting epithelium tubes are formed and are surrounded by thick mesenchyme, and the rate and extent of branching appear directly proportional to amount of mesenchyme present. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium.
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. It is notable that the differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood.
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar. postnatally from 1-3 years the alveoli will continue to form and in asa result increasing the surface area for gas exchange.
|-
|}

[http://www.nature.com/gimo/contents/pt1/full/gimo5.html/ Anatomy and development of oral cavity and pharynx]

<pubmed>22844507</pubmed>
<pubmed>5323506</pubmed>

<pubmed> 22876201</pubmed>
[http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development]

[http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063039/ How do lungs work]

==Current Research, Models and Findings==

===Current Models===

===Current Reseach and Findings===
Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:
# The Conducting system- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The Functional unit- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see above for more information for the properties of this stage). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch:

:::# Domain branching
:::# Planar bifurcation
:::# Orthogonal bifurcation
:::# Trifucation --add reference from intro

[[File:Four Models of Lung Branching.jpg|centre|550px]]

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:Lung Fgf10 expression cartoon.jpg|centre|500px]]

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.

2. '''The Functional Unit'''

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency -caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===References===
<references/>

User:Z3333429

2014-10-22T00:51:59Z

Z3333429: /* Lab Attendance */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)

Lab 11: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:51, 22 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Lab Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

User:Z3333429

2014-10-22T00:49:46Z

Z3333429: /* Lab Attendance */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)

Lab 11: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:49, 22 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Lab Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

User:Z3333429

2014-10-21T17:15:20Z

Z3333429: /* Online Assessment 9 */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)
==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Lab Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

User:Z3333429

2014-10-21T17:12:43Z

Z3333429: /* Lab Assessment 10 */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)
==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signalling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hybridisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognised using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
<references/>

User:Z3333429

2014-10-21T17:10:44Z

Z3333429:

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)
==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

==Lab Assessment 10==
'''Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis.'''<ref name=”PMID25266257”><pubmed>25266257</pubmed></ref>

'''SUMMARY:'''
Mutant zebrafish models were used to find the Rx3-regulated gene sequence involved in the patterning of the early eye. It is understood that a single family of genes is vital in the programming of the DNA sequence responsible for retinal (Rx) transcription factors. The exact gene cascades that vertebrate eye morphogenesis rely on are poorly defined and mutations in the human retinal homeobox gene (RAX) have obvious clinical relevance due to their significance in the occurrence of abnormalities such as anophthalmia and microphthalmia.

'''METHOD:'''
*AB Zebrafish were screened for heterozygous Rx3 mutations and were subsequently mated.
*These embryos produced from these matings were grown to the 8-somite stage of development.
*A dissecting light microscope was used to distinguish the embryos based on their morphologies. They were separated into eyeless mutants and eyed specimens labelled “normal’ and “wild-type” phenotypes respectively.
*Three normal replicates and one wild-type replicate were collected and stored until processing.
*The RNA was isolated with the use of a RNA extraction kit and a a nanodrop spectrophotometer was used to measure the levels of RNA in the samples. The RNA integrity number was kept constant (at between 8 and 8.8 units) with the use of a Bioanalyser.
*The RNA samples were organised in cDNA libraries using RNA sequencing kits.
*The RNA sequences were mapped to the zebrafish genome and this data was used to predict the function of novel genes.
*Gene counts were performed and compared to human homologs and human diseases with a known aetiology were linked to the zebrafish homologs.
*In Rx3 mutants, the genes hmxl and six7 were analysed and in situ hibydisation was carried out on these wild-type zebrafish embryos.

'''RESULTS:'''
Rx3-regulated genes were recognized using RNA sequencing and were found to play a role in optic vesicle morphogenesis within the wild-type phenotype. It was found that gene communication had occurred during the early eye development and hub genes (genes strongly connected via cross-talk) were found to express more changes between Rx3 mutants and normal phenotypes. The down regulation of hub genes in Rx3 mutants show the precursors for eye development and human eye disorders: homeodomain transcription factors and retinoid signalling mediators.

'''CONCLUSION:'''
The zebrafish models displaying Rx3-regulated genes showed that Rx3 was responsible for optic vesicle morphogenesis as well as the expression of homeodomain transcription factors and retinoid signalling genes.

'''REFERENCES'''
</ref>

2014 Group Project 1

2014-10-15T01:39:17Z

Z3333429: /* Current Research, Models and Findings */

{{ANAT2341Project2014header}}

=Respiratory =

===Introduction===

The respiratory system allows the body to take in oxygen and exhale carbon dioxide. The respiratory system is formed by the endoderm. The splanchnic mesoderm develops into connective tissue, cartilage and muscle of the respiratory system. The respiratory system moves the air in from the nose to the pharynx, larynx, trachea, bronchus and alveoli, which is where gas exchange occurs. During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that till about week 37 or birth is the fetal stage. However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus are in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and fill up with air automatically. The lungs do not inflate completely till about 2 weeks of the new born. The surfactant in each alveoli helps keep the lungs open and prevents it from collapsing.
The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

===Conducting Zone===

The conducting zone is made up nose to bronchioles and its function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and is where nasal cavity is lined with cilia, mucous membrane and consists of blood filled capillaries. The oral cavity id formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm lined depression, separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx forms the vestibule of oral cavity.
The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle. The bronchi is formed in week 4 and the lung buds develop and further divide each into more divisions. The left 2 and the right 3. These bronchioles will continue to divide until 17 subdivisions. After the baby is born the the bronchiole tree further divides 6 more divisions.

===Respiratory Zone===

The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli. The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli.
Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs. The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. The alveoli is where the carbon dioxide and the oxygen exchange.

=Lung Development Stages=

{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"|Lung buds would have formed and lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include the formation of extensive airway branching of about 14 or more generations of branching resulting in terminal bronchioles. The conducting epithelium tubes are formed and are surrounded by thick mesenchyme. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium.
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. It is notable that the differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood.
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar. postnatally from 1-3 years the alveoli will continue to form and in asa result increasing the surface area for gas exchange.
|-
|}

===References===
<references/>
[http://www.nature.com/gimo/contents/pt1/full/gimo5.html/ Anatomy and development of oral cavity and pharynx]

<pubmed>22844507</pubmed>
<pubmed>5323506</pubmed>

<pubmed> 22876201</pubmed>
[http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development]

==Current Research, Models and Findings==

===Current Models===

===Current Reseach and Findings===
Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract <ref>Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development</ref>. However, physiologically, the organ can be divided into two parts that occur subsequently:
# The Conducting system- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The Functional unit- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location <ref name="PMID24058167"><pubmed></pubmed>24058167</ref>.

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see above for more information for the properties of this stage). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential number of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange.

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch:

:::# Domain branching
:::# Planar bifurcation
:::# Orthogonal bifurcation
:::# Trifucation --add reference from intro

• Another recent study conducted in 2013 <ref><pubmed>24058167</pubmed></ref>, suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:FGF10 Expression.png|centre|400px]]

• A research group in 2011 <ref><pubmed>22359491</pubmed></ref>, identified two key signalling factors; fibroblast growth factor (FGF10) and sonic hedgehog (SHH). Other signalling factors such as sonic hedgehog (SHH) receptor patched (Ptc), Bone morphogen protein (BMP4) were also identified from experiments and developed a model to explain the branching network.

2. '''The Functional Unit'''

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:
:::1. Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first breath is just after delivery and hence the first time in which the alveolar serve their purpose is after birth.

:::2. Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

===References===
<references/>

<ref><Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 10, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development></ref>
<ref><pubmed>22844507</pubmed></ref>
<ref><pubmed>20692626</pubmed></ref>
<ref><pubmed>22359491</pubmed></ref>

[[File:Lung Models Normal vs. Diseased.png|600px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

'''References'''
<references/>

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency -caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===References===
<references/>

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

User:Z3333429

2014-10-15T00:26:50Z

Z3333429:

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

Lab 10: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 15 October 2014 (EST)
==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

Talk:2014 Group Project 7

2014-10-14T16:02:23Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==
===1===
Good introduction but I would move what happens in the embryonic development to the “development” section. Also, don’t forget any references and in-text citations for this section. Maybe add more on what the page is about and what the readers should be expecting. Nonetheless, it gives a good background of the key organs in this system. The diagram for the timeline of development is quite complex. Try to explain what is happening in this diagram within the “development” section. For example, maybe try to have the same headings (cell multiplication, cell migration, etc.) as the diagram for the “development” subheadings. Or, if you’re willing, make a timeline of your own. At least, you can make a simpler diagram where only relevant information is included. Good job on the “Visible Anatomical Details” table.

On current findings, good choice on research articles. They’re very relevant to the topic and to the project as well. Maybe try to add some images if possible. Also, try to add some dates or anything to show how recent these studies are. There is a bit of imbalance in terms of the amount of content for each study but nonetheless, this section was written well. Good job! As for “abnormalities”, this section was done well. Each disease was written with lots of detail but very concisely. I do suggest adding more images that show the clinical manifestation of each disease. Also, don’t just focus on the manifestations of each defects. Try to look for current treatments or techniques on managing the abnormality. Also, maybe look for more references.

On historic findings, where is it? 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”.

I’ve check all the images and there are no issues with them in terms of copyright. I can see that you tried to add captions to each photo, which is good but you can format the image in a way so that the caption is framed with the photo. Check out the [[https://embryology.med.unsw.edu.au/embryology/index.php/Help:Image_Tutorial#Image_Formatting| Image Formatting]] guide to do this. Overall, this page is very detailed and written very well. Just try to edit the page and make it look cleaner.

===2===

This project page is very nicely organised with the group clearly specifying what aspect of neural development they are covering, being the CNS. The use of headings and subheadings is done very neatly, however sections 1.1-1.5 could be subheadings for the larger title ‘system development’. The key points have been clearly described but there is no referencing throughout the ‘Introduction’, ‘Brain development’ and ‘Abnormalities’ sections. Most key points have at least some information on them which is good for this stage of the project; however some of the headings without could use some more work.

The choice of content is highly appropriate and the use of diagrams and pictures help show the groups understanding of the project thus far. I particularly like the use of subheadings in this project as they make the page look neater and organised. The image showing the timeline of fetal neural development is good however perhaps it would be better to draw or make a timeline on the computer in order to show better understanding of the time course of fetal development. Most images that have been uploaded are also well referenced and when clicking onto them, it takes the reader to a page that has more information related to the image. The table to describe anatomical details is also done well and is important that such a key point is mentioned seeing as this is an anatomy course.

I also really like how the ‘Current research, models and findings’ section is split into ‘Current research’ and ‘Future Research’, however it seems future research needs to be further looked into. The ‘Abnormalities’ section is done very well, with multiple abnormalities listed with images used to show each one. The bolding of several key words is seen and is helpful in showing understanding of some of the key points. There are also no historic findings so try and find some information on that.

Referencing is correctly done with most references being in one main section at the end, and ordered correctly. In-cite referencing is also done correctly. All images are correctly referenced with copyright information present and the student image template. I also like the way the current research findings sources have been referenced with the use of dot points assisting learning by not just presenting to the reader as a blob of information.

Overall, well done group 7! Keep up the great work!

===3===
The content looks well organized. The introduction could use a bit of work; it does a good job of introducing the CNS, but it should also mention all the other sections this page will cover regarding the topic. You might want to get rid of the using bold for brain and spinal cord, it just makes it look a little weird. Otherwise, a good embryonic developmental background is provided, it’s a good way to set the stage for when fetal development will commence from.

The information is organized well, no chunky slabs of texts. But the use of dot points is a bit extensive; almost every section of the page has dot points or makes up the complete majority of the info presented. You might want to present some of it in paragraph form e.g. the abnormalities part, as that section can still be kept quite short and not be packed with text. As long as you mention what it is, how you get it/how it forms, some statistics and use a picture, the section can be still visually appealing.
The images are captioned ok, but there is a better way of doing it. In the command to input the image, continue the command with: |thumb|’whatever you want to write’], and the section in the apostrophes will be the caption under the picture (go into edit mode on another project page for a better idea, I might not have explained well).

The use of the table is well done, makes all that info easily presentable, though I see the meninges development still needs to be done. The current research models and findings looks kind of messy with just the referenced PubMed article there. It might look better if you had the article name written in bold and a couple sentences underneath each to describe what the article was trying to achieve, like what has been done under current research. A couple pictures may be included to make it all more visually appealing and colourful.

Overall, this was done well. You have a good amount of information, just try not to present it all in dot points. Make sure all your info is referenced in text, will all references displayed at the bottom of the page. Another note, try to organise your pictures in different areas of the page as well, as they are all currently on the left hand side.

===4===

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck ☺

===5===
This page is organized well, all the headings and subheadings are thought through. Although, I’m unsure while the sections brain and spinal cord are in bold? The development during fetal period image lacks the necessary “student template” at the bottom of the description summary and I was unable to open the link http://www.nichd.nih.gov/publications/pubs/acute/images/p44.gif.
Otherwise, all the other images uploaded on the page look really good and are referenced correctly.

The table under the section brain development is very brief, and expansions on the content will allow for a better understanding of the content. Adding images to appear after the table will also add to the appearance of the page and give it a cleaner look.

The spinal cord and menegies development have been left untouched and the current research models have no content, just pubmed references. I understand the current research models are probably the hardest part of the assignment, but the content appears to be quite good, the formatting of the section could be improved by following the structure Mark uses. You could look at the other group projects as examples.

In regards to referencing, there are no in-text citations for the first two subheadings. I would also like to recommend just adding a final list of references at the bottom of the page, as it looks much neater.

The abnormalities section is done well. But try to minimise the use of dot points as this section lacks any structured paragraphs. It use of images are great, although there is an image that appear to have been removed and as a result, there is a broken link.

Overall, great job so far!

===6===
This is a really good project so far. The introduction is really well done and I especially like that you have included a diagrams in it. The brain development is good, however I’m not completely sure about the dot points. It would look better if they were not there.

Well done with the images that you have got there they all appear to be well described and referenced when you click on them. Only problem with the images is that there is a lack of them. It appears that there is an imbalance between written information and images tipping in favor of the information. I think it would be a good idea to add some more images to elicit more excitement in the page. Student images are a good idea as they highlight that it is a student project and make it more interesting for the viewer.

The current research models and findings shouldn’t be left like it is at the moment. You will need to go into more detail and reference properly. While on referencing it is important that you put all your references at the bottom of the page. You only have 20 at the bottom at the moment and it is clear that you have used many more than twenty. Also you need to add in text citations so that we know exactly where you have got your information from.

The current research part is good with plenty of information, but again look at adding more images to make it a bit more interesting. There are obviously some parts that you need to finish off which I’m sure your aware of.

Overall it is a really good project with the potential to be excellent because of the amount of effort you have put into the research. Just make sure you change your references so that they are all down the bottom and have in text citations, add more images and maybe student images as well to make your page more presentable. Very well done so far and good luck with finishing the project off.

===7===

In this review I intend to highlight the merits of your project and suggest some areas for improvement in light of the marking criterial provided.

The introduction provides the perfect preface for your project, it serves to summarise the topic and highlight the areas that you will be addressing.

In the first section you have discussed fetal development of the neural system in great detail. I feel that a lot of research has gone into the collection and presentation of this date. The diagrams have been appropriately selected. Each image really ties in with the content and helps explain that stage development; I particularly like the diagram summarising the cell migration. In addition the images are well referenced. In the link you provide a brief description of the image and effectively explain the meaning of all the abbreviations.

The topics addressed under the heading of current seem quite interesting. The project really succeeds in providing insight into this new MIR technology, a technology that will certainly allow us to build on current knowledge of fetal neural development. I see that the heading of future research has not been completed. However I feel that this is a very interesting sub heading and shows a clear aspiration to go beyond the scope of the course.

A number of abnormalities have been addressed. I only suggest that you ensure that each of these subheading is addressed for each abnormality. Description; Epidemiology; Cause and possible Treatments, an image would be good too.

All the content on this page is well written. I feel that all the subheadings are relevant, though some sections are not complete. The only major drawback of your project is that, at this point the area of historic findings has not been addressed at all. Make sure you address this area.

===8===

I believe the introduction of this page is excellent. A good choice of appropriate headings and subheadings. The addition of images would just add to the presentation of the introduction.

The development section of this page is excellent! There is very informative, easy to follow and well-presented. There is clear evidence of significant scientific research and correct referencing. The choice and use of graphs and diagrams is excellent and does indeed add to the overall understanding of this section. I do believe, however, that this section could be included with the use of more tables? (Eg. The first four bolded subheadings)- but this is only a suggestion. Excellent nevertheless. Really enjoyed the ‘Visible anatomical details’ table.

The current research section is a bit lacking in detail and appropriate choice of pictures. There is a good choice of subheadings and references though. The first included study is excellent though and should serve as a benchmark for the other remaining studies.

The historic findings section is not presented on the page yet? I cant seem to find this section on your page.

The abnormalities section is excellent, well presented and well researched. There is a very good use of subheadings and an excellent varying amount of abnormalities/defects included. The use of dot-points is effective, as well as, the accompanying pictures- really aids in understanding. This section, however, needs to be correctly referenced and cited. The other remaining abnormalities should be finalised (although I believe not all of the abnormalities should be discussed in great detail!). Great work, overall.

===9===

Overall, the project contains a decent amount of content as it is, split up into appropriate subheadings, considering the large scope of the nervous system. The introduction provides a succinct description of the CNS, however including an outline of what topics the page intends to cover would be good to orient a reader that approaches the page for the first time. The descriptions of the brain and spinal cord are well-written, however require in-text citations and some words need not be capitalised e.g midbrain, hypothalamus. These can be easily fixed with proof-reading and further editing.

The use of an image to illustrate fetal development was a very good idea; although the diagram is itself seems complicated, it can be explained well with the accompanying text beneath. The segmentation of the timeline into 4 different parts made it easier to follow, although I would consider placing the images on the right hand side of the page to reduce the vertical length of the page and the scrolling required to navigate through it. The section on ‘brain development’ contained some relevant information, formatted in dot points which improves readability, however in-text citations are needed to allow the reader to source the information if required. The use of the table in this part was effective also; it was concise and straight to the point.

Although the brain development section was very well detailed, there was no information in the spinal cord and meninges sections; with further research, these need to be evened out, along with the current findings section which is just references at this stage, but still a good start to finding sources of information. The section on current research is well-detailed and contains a lot of information too, which is good to see. Fiinally, I thought the section on abnormalities was very well done, using subheadings to segment the content. The use of dot points allowed the information to be easily read off the page, and use of images to accompany them helped the reader to visualise the conditions. There is one image however that has been incorrectly uploaded; consulting Dr Hill’s Wiki help page can remedy this. Also, the placement of all references under one list at the end of the page was effective in neatening it up, that was very well done too.

Overall, the project’s content has been well-researched and there is evidence of good teamwork and communication. Perhaps the use of some student-drawn images and inclusion of a relevant video may be areas of improvement.

===10===
This project is coming along quite nicely! The introduction is very thorough and provides a really sound basis for the topics which you covered. I enjoyed the use of diagrams in your introduction- although I admit your flow diagram was very scary! I think you should be a bit more clear in your timeline of the human neural development – it took me a moment to figure out what was happening, so it may be a better idea to put all this information into a table.

The images that you have used are great as they are relevant and provide interest to your project page. The referencing on them appears consistent and there doesn’t appear to be any copyright issues- so I think you should include a few more diagrams, just to make your message even clearer.

The current research models could do with some reformatting. I don’t think it is a good idea to put the references at the start, and secondly it seems like your work is not so well structured. I think if you included some bullet points in your work, it would greatly aid the clarity. The abnormalities is off to a good start, I see that it is well researched but you want to consider adding some more pictures or diagrams just to make it a bit more visually appealing. Overall this project is off to a good start, I think it may be a good idea to leave all your references until the end just to make your work more cohesive.

===11===
Very good introduction! Very informative and gives a great jist as to what the project will be about. The developmental timeline is very well done and easy to comprehend and understand. You should add a lot more pictures in general to the whole page, there’s a lot of information and is organised nicely.
I feel the usage of dot points is a bit excessive, maybe try to organise some of the information into paragraphs to make it match the wiki page style. The references aren’t organised at the bottom of the page yet; maybe something for the group to start when the page is unlocked for editing? Some parts of the page still do need a lot of information still to be added.
I think you could go more into detail with the brain development; maybe you could make sub sections for development of the cerebrum, cerebellum, brain stem etc to add more information.
I’ve noticed that there is an image that hasn’t been uploaded correctly; have a look at the page on how to upload pictures, I’ve found that using Mark’s tutorial has been really helpful when I was doing my page. Hope this helped!

===12===
Introduction is a bit too focussed on anatomical division of brain and spinal cord, doesn’t address current/historical research or abnormalities. Change the word “website” to page or project. The embryonic development is explained well and should have its own subheading. Referencing is required for the whole of the introduction, Brain development and abnormalities sections. The Sections 1.1 through to 1.5 could be subheadings under the “system development” main heading.

Image showing fetal development timeline is quite overly complex and captioning/referencing is required. Additional explanation of the timeline image narrowing the viewer’s focus onto key fetal development processes will provide greater clarity allowing them to relate the image to surrounding content. The 3 images included in the project also are absent of referencing/captions present on the project page, though info after clicking on the image is great. Brain development information is in-depth and well presented(great use of table), the Spinal Cord and Meninges section have content yet to be added. There is an unusual caption [11] at the end of brain development which should be removed. Like the focus on anatomical structures.

There is an absence of historical research which could be found searching on Pub Med for studies completed before a certain date(1970 for example). Current Research content is sufficient. Removal of the different types of dot-points, with addition of images would make the section more attractive.Abnormalities content is great for sections covered, removal of surplus abnormalities and “500px” at the bottom of the section is need unless they are still to be added to.

===13===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

--[[User:Z3418981|Z3418981]] ([[User talk:Z3418981|talk]]) 14:21, 16 August 2014 (EST) Hey everyone,

What's everyone's ideas about doing the neural system for our project? there are lots of interesting Neurologic deficits that we could talk about!!!

--[[User:Z3419587|Z3419587]] ([[User talk:Z3419587|talk]]) 23:25, 16 August 2014 (EST) That's a good idea. Neural system is a complex structure and it should be fun to work on it! Any other ideas?

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 23:51, 19 August 2014 (EST)
I talked to Yas before, sorry couldnt respond faster haha. Agree that Neural system would be interesting to research :p

Do you guys have facebook as well? It might be an additional way to communicate

--[[User:Z3422484|Z3422484]] ([[User talk:Z3422484|talk]])
I also agree on this topic being quite interesting as well
--[[User:Z3418981|Z3418981]]

--[[User:Z3418981|Z3418981]] ([[User talk:Z3418981|talk]]) 10:54, 25 August 2014 (EST) hey guys it's yas! so we each need to choose one of the following:
Review the neural system development during the fetal period.
Identify current research models and finding.
Identify historic findings.
Identify abnormalities that can occur in this system during fetal period.

--[[User:Z3419587|Z3419587]] ([[User talk:Z3419587|talk]]) 21:07, 25 August 2014 (EST) Thanks! This is vivian. Can I do "the review of the neural system development during the fetal period"? Or if anyone wants to do this section?

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 12:07, 26 August 2014 (EST)
Hey guys, Can i do historic findings for fetal neutral system development :) - Sean

--[[User:Z3419587|Z3419587]] ([[User talk:Z3419587|talk]]) 17:47, 26 August 2014 (EST)I have put some subtitles to give a brief structure to our webpage, feel free to change them if you want!

--[[User:Z3418981|Z3418981]] ([[User talk:Z3418981|talk]]) 17:51, 26 August 2014 (EST) sure and I'll do the abnormalities - Yas

--[[User:Z3419587|Z3419587]] ([[User talk:Z3419587|talk]]) 18:25, 26 August 2014 (EST) hey Yas, see if this helps. <pubmed>25007063</pubmed>

--[[User:Z3418981|Z3418981]] ([[User talk:Z3418981|talk]]) 21:14, 26 August 2014 (EST) Thanks Vivian!! the article is very helpful! and the page looks really good too :)

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 20:18, 26 August 2014 (EST)
Hey guys, I think the last entry from my section will help alot in the ''Development'' section for our project :) - Sean

<pubmed>17848161</pubmed>

--[[User:Z3419587|Z3419587]] ([[User talk:Z3419587|talk]]) 23:14, 26 August 2014 (EST) That's true! thanks Sean :) - vivian

--[[User:Z3422484|Z3422484]]--[[User:Z3422484|Z3422484]] ([[User talk:Z3422484|talk]]) 12:50, 27 August 2014 (EST)
Hey guys, this is a useful article for the abnormalities area

<pubmed>24664314</pubmed>

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 23:55, 1 September 2014 (EST) nice one :D
How are you guys going with your sections?

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 12:58, 17 September 2014 (EST) <pubmed>10226791</pubmed> maybe for development

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 21:12, 20 September 2014 (EST) http://www.ehd.org/cache/pdf/fd7e47f291dded855c38ffb3418fbdc8/timeline.pdf

something which might help us figure out a timeline structure

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 11:56, 24 September 2014 (EST) http://discovery.lifemapsc.com/library/review-of-medical-embryology
A textbook which has great information on the development of the CNS during the fetal period

--[[User:Z3422484|Z3422484]] ([[User talk:Z3422484|talk]]) 11:35, 8 October 2014 (EST)
Hey guys i will be adding a few extra research articles to the current research tab

--[[User:Z3422484|Z3422484]] ([[User talk:Z3422484|talk]]) 11:35, 8 October 2014 (EST)
Also is there anything else anyone needs help on as well?

--[[User:Z3422484|Z3422484]] ([[User talk:Z3422484|talk]]) 12:09, 8 October 2014 (EST)
Forgot to mention that I'll also be adding spinal cord abnormalities

For Historial Research and Findings
<pubmed>19339620</pubmed>
<pubmed>8005032</pubmed>
<pubmed>9311417</pubmed>
<pubmed>17848161</pubmed>
<pubmed>12768653</pubmed>
<pubmed>17060425</pubmed>
<pubmed>21042938</pubmed> for brain de

abnormalities
<pubmed>12454899</pubmed>
<pubmed>25007063</pubmed>
<pubmed>16530991</pubmed>
<pubmed>7504639</pubmed>
<pubmed>19651588</pubmed>
<pubmed>25135350</pubmed>
<pubmed>25128525</pubmed>
<pubmed>24397701</pubmed>

----

*Good start on the introduction. Maybe have it used to explicitly state what your entire page will be covering rather than just a background on what the CNS is.
*You're missing references for the huge chunks of information in the introduction section
*The image of the timeline of development seems overly complex and I can't tell if you've explained it. If it's not relevant, maybe just come up with your own concise table of what happens during the course of development
*Maybe think of re-creating some simpler images by hand and uploading them. That way you can choose to focus on what you actually need from the image to show what you're explaining
*Include the years of when your current findings were discovered
*For the "abnormalities" section, as there are many, maybe the amount of detail you've included for the first couple of ones isn't needed, but of course, use your own discretion to how much is relevant. Otherwise, the bullet points are a good way to simplify information
*Collate all your references in the bottom from all the separate sections

Talk:2014 Group Project 8

2014-10-14T16:02:22Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==
===1===
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.

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!

===2===

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.

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.

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.

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.

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.

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.

===4===

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.

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.).
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 :).

===5===
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!
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.

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.

===6===
Musculoskeletal
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.
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.
Sections for historic findings, current research, models and findings will need to be added.
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?
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!

===7===

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).

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.

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.

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.

===8===
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.

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.

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.

==4==
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.

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!

==5==
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.

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

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.

The abnormalities section also seems to be coming along quite well. Keep up the good work.

==6==

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.

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.

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.

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.

This page has no information for the “recent findings” or “historic findings” section. Remember to include relevant information/pictures and references to these sections.

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.

==7==
In this review I hope to highlight the merits of your project and suggest some areas for improvement in line with the marking criteria.

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.

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.

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.

Finally it would be good see some images to support the text. Perhaps diagrams on tendon development would help summarise the process.

Great work so far!! Hope this feed back helps.

==8==

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.

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.

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.

Week 5

--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 22:34, 26 August 2014 (EST)
Hi guys
After discussing in lab last week we tried to divide the categories and work as following;
* skeletal and cartilaginous development - Joel
* muscular development - Gowtem
* overall skeletal and muscular arrangement macroscopically - Danny
What do you guys think about addressing these topics as well
* Historical findings
* Abnormalities
* New findings

--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 12:44, 27 August 2014 (EST)
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

--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 01:02, 28 August 2014 (EST)
I would suggest that we narrow down the topic to focusing on the appendicular musculoskeletal system, so that;
*To make work load more managable
*To avoid the multiple highly specialised and irregular muscles/bones of the head
*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.
*Joints and tendons are included in the musculoskeletal system, we should about wether we want to have a section for them.

--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 09:05, 31 August 2014 (EST)

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

--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 14:57, 9 September 2014 (EST)
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.

--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 01:51, 10 September 2014 (EST)
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.

--[[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&pg=PA38&lpg=PA38&dq=primary+secondary+myofibers&source=bl&ots=RSRcVVe5xr&sig=eDJBF_3qkYzA8WSin1tnbzT2xYY&hl=en&sa=X&ei=OegYVL_UHpOB8gWMxoDYAw&ved=0CCoQ6AEwAw#v=onepage&q&f=false

--[[User:Z3418989|Z3418989]] ([[User talk:Z3418989|talk]]) 12:27, 20 September 2014 (EST)
Ill add a bit more on embryonic muscle development guys

--[[User:Z3418779|Z3418779]] ([[User talk:Z3418779|talk]]) 22:30, 6 October 2014 (EST)
Here are some article which would probably be helpful
Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo: Nrk2b and NAD+ in muscle morphogenesis
Coexpression of two distinct muscle acetylcholine receptor a-subunits during development

At the moment I have a general structure for tendon development and abnormalities will add to wiki tommorrow.

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

Talk:2014 Group Project 6

2014-10-14T16:01:28Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

This project would greatly benefit from an introduction, to present the contents of the project. The content is broken up into individual organs, of all the systems endocrine definitely one of the most varied in location so this approach does have some merit for initial data gathering. It does present the problem for viewers in navigation and resulting in continual repletion of timelines. Each organ is subdivided into timeline, introduction, structure, function, development and abnormalities. The content presented is solid and obviously well referenced. Placenta section should be added, because of its significant endocrine organ during fetal development. The references are mostly placed at the bottom of each organs section, these should be moved to bottom of the whole project in combination with in text citation. This will make the body of the project less cluttered and more fluid.

The table for hypothalamus hormones and associated abnormalities are mostly incomplete with “Example” filling many of the boxes. I would advise completion of hypothalamus hormone table and removal of associated abnormalities. In total there were only 3 images, addition of 2+ more images would help readers visualize the developmental organs. With at least one image per organ and preferably an additional image for an abnormality. Sufficient content is presented in this project though significant formatting changes are needed to create a completed project, additional images would be preferable.

----

Overall, this is quite a good project considering the complexity of the system. I think that generally, this project would benefit from some restructuring, so as to improve the cohesiveness of your work. I think that an introduction is a good idea to organize your ideas and give the reader a good background when trying to understand some of the more difficult concepts. I think that the choice of sub headings should be advised. It is interesting that you have chosen to deviate from the given subheadings, and I understand for your system that that may be necessary- however I think that some structure or regular subheadings for each part may be a bit easier to control. Also I think an overall timeline is always a great idea as it provides a visual representation and puts things into perspective.
I also think that some areas could use a bit more research, for example a large part of the pineal gland and hypothalamus appears to be missing and there are kind of “insert text here” sections- which I’m sure you’ll work on by the submission date.
I also think its important to remember that your referencing needs to be carefully done and consistent. Currently it seems quite poorly organized, and I think overall could use with a few more resources for every section. I think because you are already deviating from the normal structure of things, it would be a good idea to leave your references until last, just so your work isn’t broken up even further. The abnormalities section is severely lacking- the table is a good idea, but make sure you fill it!
Overall a good start, some places need some serious content others just need a tidy up.

----

Great job on doing the endocrine system! There are lots of content for each organ of this system, which is good. I can see that this system was broken down into organs and allocated to different members. The only problem I see with this format is that presentation could be incoherent. I suggest try to follow the outline Dr. Hill gave us like development, current findings, etc. and just break each section into sub-sections for each organ. If that’s too much, then maybe just a single timeline of the development of the whole system. Also try to have a uniform layout for the tables about the hormones secreted by each gland.

There aren’t many images used in the page so maybe try to add more images. They really help with getting the readers to understand the information. In terms of referencing and citations, good job on choosing the research articles. All of them seem to be relevant to the the project. Don’t forget to use in-text citations. Not only is it important but it will make the page look a lot cleaner. Also, try to get all the references into one bulk at the bottom of the page. Overall, there aren’t a lot of problems in terms of the content but mainly about organising the page, making it coherent, and cleaning it up. I think the thyroid, parathyroid, pancreas, and adrenal sections were remarkable. Well done!

----

Group Project 6 – Endocrine Development

An introduction could be very useful to summarise what the page is going to discuss. Sections 1.2-1.11 could all be subheadings under the main heading ‘System Development’, and then each of these subheading could be further divided into smaller subheadings with timeline, introduction detailing structure/ function of the endocrine organ. It is however very well done how the headings of each organ are then further subdivided into ‘abnormalities’, ‘research findings’ and ‘timeline’. However, the fact that each section has its own references and is subdivided as such, shows that even though the page may appear more ordered, there appears to be little communication between group members at this stage. So perhaps a goal could be to make the page look like one flowing work piece as opposed to sections that each person has done.

I think the content is very well researched and I like the way each organ of the endocrine system is discussed, as all are important in fetal development. The use of images is appropriate and very well done as they are referenced correctly and when you click on an image it takes you to a new page showing the student image template, copyright information as well as extra information regarding the image. There are no student-drawn images however, so perhaps it could be possible to draw a flow chart perhaps of gonadal fetal development. The use of tables is also done very well and is frequent throughout the page, with some being used to illustrate the anatomical development of certain organs, for example, the adrenal gland and pancreas. The graphs are also useful in portraying information from research findings.

The project page is missing information regarding historic findings, and I think that if this page is going to have a main heading for Abnormalities, then the group should put all their information regarding abnormalities under this section. Although it is not an endocrine organ that grows within the developing foetus, but is an important part of the mother, there is not much information on the page regarding the placenta. This section needs to be completed as the placenta is an important source of hormones and acts as an endocrine organ during the pregnancy, sustaining the foetus.

It is good that there are many references, indicating thorough research into the endocrine system with each organ heading have its own sources, however I think these references need to be ordered better. The actual referencing is done correctly, however in-text referencing is absent, so it may be best to fix this. Most images are referenced correctly as well.

Overall, keep up the good work, but just edit the page to make it look neater and finish the sections you need to.

----

At first glance, a lot of sections seem to be incomplete. On second glance, I’ve noticed that you have added all the headings used by other groups (timeline, current findings, abnormalities) as subheadings for your own project, which I think it a really smart idea. Because you have so many glands that need to be covered, writing these sections separately can be confusing with the information quickly becoming muddled up. Doing it this way eliminates that confusion.

Make sure the use of tables is appropriate, using a table for one row of info is kind of pointless (pineal gland). The timelines used should also start with the week number, otherwise it can be quite confusing trying to work out the time (e.g. try not to say times such as ‘by the second trimester’). The information presented was concise and to the point, no long-winded explanations or slabs of text which was good. The images used were relevant and captioned.

Concerning the work completed, overall it was done well. A lot more work still needs to be completed however. References should also be made in text. If you are unsure how to do this, just go into edit mode in another group’s project and see how they have done it, instead of listing all the references at the bottom of the corresponding section. Make sure all the references are also presented at the bottom of the page, not separated into sections. It would also be nice if more images are used, if not one image for every gland then at least one for every second gland mentioned (it just needs more images).

------

There seems to be no introduction on the page, don’t forget to add content to this section before the final submission. The overall page looks disjointed by the choice of sub-headings. I think an overall timeline is needed to know which glands/organs develop when and originate from where. It would look much neater and would be easier to follow.

The parathyroid gland and pancreas seems to be the only sections that are properly completed. Both sections have good use of images and the tables provide easy readability. The images are all properly cited, good job.

The overall referencing of the page is all over the place and lacks in-text citations. I suggest you go through the contents and add these where necessary. If you are unsure how to do this, just look at the handout Mark gave out in week 2 for further reference. Or, alternatively you could look at some of the other project pages in edit mode. I would also suggest you leave all the references to the end of the page by simply putting </references> at the bottom of the page, as it looks neater to have them all in one place, rather than at the bottom of each sub-heading.

The abnormalities section is lacking content and there is only 2 diseases listed, with no description.

Overall, the page has good content, just needs to be edited to put in-text referencing. Some sections need contents such as the placenta and adding images to the page will also improve its presentation.

-----
So far you have made a good start. The introduction is a really important part of the project so it’s important that you get that down. The pineal gland part has made a good start but it would be good if some more hormones could be added. I think it would be good maybe if you all combined all of your times line and put them at the top of the page. You could maybe do this in a table form, but it’s certainly something that would make the project more succinct. Also instead of having references spread all over the page it would be a good idea to put the all of them at the page to make the page look more neat and tidy.

The hypothalamus part also needs to add extra information on the hormone part and add their illustration. I think it may be a good idea to add a student image because this makes the page more interesting and people looking at the page will be instantly attracted to this. Something that is really important and goes for the whole page is that you need to do in text referencing, as having the references at the end of the writing is tough because we don’t know which parts came from where.

Its good that there is recent findings in the hypothalamus part but I think this probably highlights the biggest issue with your project, being that It probably doesn’t link with all parts that well. I think it would be good if you could link all parts of the endocrine system together to make it easier to understand. For example, if you put the recent findings as a whole new part then everyone puts their recent findings in there it will make it easier to understand and look more collaborative. Also there is an imbalance in written information to pictures which tips in favor of the information. While it’s great to have a lot of information it becomes a bit boring just reading all the time so I think adding more images, particularly student drawn images would be something that would definitely improve the page.

Overall it has been a good start but the main points that need to be focused on are to finish off the information, make sure you correctly reference with in text citations and putting the references at the end of the page, and adding more images to make it more interesting. Good luck with the rest of the project.

-----
There is no introduction! You should definitely add one!
The graph in the pineal gland only has one rows; I suppose you are planning on adding more rows and hormones secreted by the pineal gland? If not, maybe just scrap the graph in general cause there’s really not much point. The graph in the hypothalamus section doesn’t have any examples yet, I presume that you’ll be adding stuff soon?
The overall project having been divided according to the each endocrine organs is really nice.
Hardly any work has been done yet on the pituitary gland yet, you might want to get started.
Beautiful work on the thyroid, parathyroid and pancreas; easy to understand the paragraphs, and they are visually aided with pictures. For the development of the adrenal glands, and the testis and ovaries, I think you should find a picture.
Historic findings, placental development and abnormalities are basically non-existent, which are vital components to this project.
Overall, the project is very very informative and very well done! The page has good content, just add the in-text referencing, and maybe try to improve the aesthetics to make it more appealing to your readers. Good luck group 6!

-----

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/> .

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck ☺.

----

Just must say, this must be one of the hardest topics to cover! Excellent work overall and continue to work hard in completing and finalising this page. But please don’t forget to add an introduction which clearly lists the outcomes that the page will hope to address

I really believe that this page would greatly benefit by re-structuring the entire layout by the headings suggested to us- ie. Development timeline, recent findings, current research and abnormalities. Seems a bit disjointed and is hard to follow.

Due to the manner in which you guys have subdivided the sections via organs, it is hard to comment and critique via the headings suggested. Some organs have been excellently covered (pancreas, thyroid, parathyroid), however, some organs do need a bit more development (eg. Pineal gland). Also, due to the way you guys have decided to approach this page, the writing styles and presentation of information does have notable differences amongst the oragans.

Overall, there is an excellent choice of headings and subheadings though. There is also excellent and correct citing in most of the sections. However, this page could be greatly benefited by re-structuring the entire page to follow the suggested headings. I really believe that the information and research included in this (hard) topic is excellent and demonstrates significant scientific research, however, the overall structure makes it hard to follow and understand! I believe re-structuring will address a lot of the issues mentioned. But again, excellent work so far in this very hard topic!

----

In this review I intend to highlight the merits of your project and suggest some areas for improvement in light of the marking criterial provided.

I believe that an organ-by-organ approach to this section is great. This really helps organise the information. This layout also makes the page easy to navigate allowing students to directly refer to the section that they want to learn about. However by doing so I think you may have neglected some of the areas.

Each endocrine organ has a great introduction describing the structural features and nature of the organ. I suggest including an image or a hand-drawn diagram of each gland and location, as this would really aid understanding The time line is a great way to summaries the major stages in development, I feel that this section has been completed with sufficient research and detail.

The section on abnormalities needs to be completed, even if only one abnormality is addressed make sure you include information on the following areas. Epidemiology; Description; Cause and Treatment. Furthermore ensure that the section on current research and historical findings is researched and addressed addressed.

I feel that your project is incredibly cohesive and attempts to provide a through summary of all the main endocrine organs. However a number of sections are yet to be completed. You have a great template right now. If all these areas are completed the project will be a success. In addition; I suggest placing all the references at the end of your project page, under one heading. Good Luck!

----

The endocrine system is made up of different glands and there is so much information that could be provided regarding the the anatomy and development of each gland so very well done for working on the difficult system! I like how you have divided the page into different glands; I can imagine having the four major headings (development, historic findings, current research and abnormalities) and then subdividing it into different organs would be more confusing. Just try to follow the same structure for each organ; I recommend doing a brief introduction, anatomy, function, timeline, development, historic findings, current research and abnormalities for each organ. It is important that your page has a coherent flow by following the same structure for each subheading. An overall introduction on endocrine system might also be very useful. You can then include in the introduction how you are planning to structure your page.

The content and number of references show that extensive research has been conducted. It would be great if you could use in-text referencing and place all the references under one subheading at the end of the page. Arranging the information into tables is a great idea but you need to complete your tables for pineal gland, hypothalamus and placenta. You also need to include more images in your page (you can include at least one image for the abnormality associated with each organ). There are a few images included at the moment and they are well done and appropriately referenced. You can also try to draw your own diagrams. In my opinion, a timeline showing the development of all the systems would be a great way to compare the different stages in development of different endocrine glands. Maybe think about including this in a table after you finished all the sections; it is a good way to connect the information provided separately for each organ. Overall the content of this page is very good but it needs to be formatted so that it can have a coherent flow. Also there is no information for introduction, historic findings and development of placenta, make sure you include those.

----
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

----

== Group Project Topic - Endocrine ==

--[[User:Z3414648|Z3414648]] ([[User talk:Z3414648|talk]]) 11:17, 20 August 2014 (EST) We have chosen our group project to be on the endocrine system.

--[[User:Z3418702|Z3418702]] ([[User talk:Z3418702|talk]]) 13:07, 20 August 2014 (EST) We have decided to allocate 2 topics (endocrine organs) to each group member. We will go and research each and look for research articles and then figure out the best way to structure the content.

--[[User:Z3414648|Z3414648]] ([[User talk:Z3414648|talk]]) 12:19, 26 August 2014 (EST) This is a draft allocation for research topics for our project.
Janaki - Pineal, Hypothalamus.
Ali (z3414648)- Pituitary, thyroid.
Samrah (z3418837) - parathyroid, thymus, pancreas.
Ruth - Adrenal, gonad, placenta.
Samrah and Ruth if there is heaps to do on those three parts that i've allocated just let Janaki and I know and we can also help out. If anyones topics are sparse on info also let us know and we can reshuffle the allocations

--[[User:Z3418698|Z3418698]] ([[User talk:Z3418698|talk]]) 22:02, 26 August 2014 (EST) Hey guys, I was thinking we should maybe have a heading 'Recent findings' for maybe a few of the topics and have a short, brief summary of any new developments. I think it would be really interesting!

--[[User:Z3418702|Z3418702]] ([[User talk:Z3418702|talk]]) 00:00, 27 August 2014 (EST) That's a good idea, should we put a separate section on recent findings, or just some information on recent findings under each section? Also we need historical findings

--[[User:Z3418837|Z3418837]] ([[User talk:Z3418837|talk]]) 00:44, 27 August 2014 (EST)Hey guys, it's better to post student numbers to the parts allocated to each group member so it's easier for the tutor to mark. I would do this but i'm not sure about who is who :P Also I like the idea of recent findings. I think it's also better to post articles related to the recent findings and abnormalities as we go along as this will make it easier instead of leaving it to the end. For now, I think we should just post up as many articles related to each topic as possible and then figure out how to structure the content.

--[[User:Z3414648|Z3414648]] ([[User talk:Z3414648|talk]]) 21:22, 2 September 2014 (EST) Hey guys, I've done some research on the prenatal development of the thyroid gland so I'll add that to my section. We can always change it up later.

I also found this review article that goes into a lot of detail about the pituitary gland. It explains the cellular differentiation involved to create the cells responsible for manufacturing hormones like ACTH. There is a lot of complex gene involvement but I was thinking we could condense a lot of the information into a table. I suggest you guys do that for your organs too rather than having a lot of jargon on our page that only an advanced biochemist will understand.

<pubmed>22872762</pubmed>

--[[User:Z3414648|Z3414648]] ([[User talk:Z3414648|talk]]) 10:09, 9 September 2014 (EST) Hey i found a great article on normal and abnormal thyroid development and it's given me a lot of great information for the timeline part.
<pubmed>10.1016/j.beem.2013.08.005</pubmed>

--[[User:Z3418698|Z3418698]] ([[User talk:Z3418698|talk]]) 12:44, 10 September 2014 (EST)We are going to incorporate the Timeline and Abnormalities under each individual sub heading rather than at the end of the page. We are also going to find image links and post them in the discussion page before uploading them. We are also going to tabulate the hormones released by the glands under the subheadings. This will summarise the function of the glands in the embryo and how they contribute to fetal development.

--[[User:Z3418702|Z3418702]] ([[User talk:Z3418702|talk]]) 00:46, 17 September 2014 (EST) Hi guys, I've added some info about adrenal development through gestation, at this stage some simple dot points which will probably be expanded upon later. There is a lot of content about the cell morphology at different weeks but I'm not sure as yet whether it's necessary to include that level of detail?

--[[User:Z3414648|Z3414648]] ([[User talk:Z3414648|talk]]) 12:59, 17 September 2014 (EST) Hey guys, i found this link for an image that i'm thinking of using on the project. It's from PLOSone which is good because it's free to use those images. This is the link for it: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016752

--[[User:Z3418698|Z3418698]] ([[User talk:Z3418698|talk]]) 13:06, 17 September 2014 (EST) Hey guys, I found this image I wanted to use for hypothalamus development in a rodent, it basically illustrates the different nuclei in the hypothalamus once it it fully developed but I will be focusing on those that are present during development and the role of hormones each of them releases.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082685/figure/fig1/

--[[User:Z3418702|Z3418702]] ([[User talk:Z3418702|talk]]) 23:50, 23 September 2014 (EST)--[[User:Z3418702|Z3418702]] ([[User talk:Z3418702|talk]]) 23:50, 23 September 2014 (EST) Hi guys, I think I might use this image (figure 3), it's from the PLoS too so totally fine to re-use and shows the fetal adrenal gland using 3 different techniques, like MRI, gross imaging and histological stain. I like it because it shows the gland from different perspectives. I'll upload it soon but here's the link:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075511

--[[User:Z3418837|Z3418837]] ([[User talk:Z3418837|talk]]) 03:29, 24 September 2014 (EST) I might use this image for the pancreas section http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007739 . It basicallys shows the development of the islet of langerhans and the ratio of alpha & beta cells at different phases of fetal development. Also Z3418698, I don't think that image can be used as it has copyright restrictions. Try looking in Plos One =]

----

*Firstly, props on choosing the endocrine system. It seems like one of the harder ones to take on
*I don't understand why you chose to divide tasks based on endocrine organs as that has seemed to cause your research to become really disjointed. I guess now work harder to collaborate your separate findings particularly for things like having 1 united timeline overview
*Ensure uniformity throughout the page with little things like is it "fetal" or "foetal"? Choose one then go with it
*Maybe have labels for tables more distinguished as being separate to the main text
*Include the references throughout discussion, rather than a collection at the end of each section. Then have the entire reference list at the bottom like all the other pages have. You can look at the "edit" of other pages to copy and paste the codes
*Your timeline isn't really a timeline if there are no times mentioned in the "pineal gland" section. Try using a week-by-week format and separating information that way for all of your findings altogether. Then format that into a table
*Proofread for typos "Abnormalities" in "pineal gland" section
*Need more images for earlier sections
*Great formatting of images and tables for the adrenal gland, parathyroid and pancreas sections

Talk:2014 Group Project 5

2014-10-14T16:00:43Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

Group Project 5 – Integumentary Development

This page looks very neat and well organised, with an introduction that explains exactly what is going to appear and be discussed on the page. The Development Overview section is very well done, with the appropriate use of subheadings and content. The use of dot points is very effective, making the page look neater. Perhaps it would be good to draw a histological diagram of the skin layers, and uploading it to the skin development section. Specialised cells or important names throughout the page could be highlighted in bold or underlined as well, to highlight important terms and make it easier to learn and remember from. The title ‘Some Recent Findings’ accurately portrays what we as students can only do, which is identify SOME of the recent findings. This section could have more than 2 recent findings however and could be further subdivided by subheadings into the different components of the integumentary system – perhaps have 2-3 research articles for each component of the system. Historic findings are well researched but some more information would be good. The ‘Abnormalities’ section is so far the best looking section as it seems it is almost completed. Perhaps a few more abnormalities would be even better.

The table of the timeline in the ‘Development Overview’ section is superbly done and the use of histological images is fantastic as it provides the anatomical information visually. When I clicked on an image however, there was no proper referencing of the image and the copyright information and student image information was not present. The images are described very well.
One image has a problem and is present in red writing, so might need to remove this as something is wrong with the file and it could not be uploaded. There are no student-drawn images and I think if this group did this, it would really benefit their project and emphasise their understanding.

The ‘Some Recent Findings’ section has a purple background, which makes the page look more aesthetically pleasing and less monochrome. I like the ‘More recent papers’ box that can be expanded to reveal any more research papers related to the integumentary fetal development, in case anyone wants to have a further read- very clever.

Journal articles are correctly referenced but website references need to be improved upon- to find how to do this go to the ‘How to reference’ page. References are all over the place and need to be compiled under each heading or one main heading titled ‘References’ at the bottom of the page.

Overall, this page is looking fantastic at this point in time so keep up the great work!

----
Introduction is short though luckily few words can go a long way, with all sections of the wiki page being properly addressed. Development overview content is good; the use of table integrated with pictures allows viewers to visually grasp the progression in skin and teeth development. The changing between dot-points and paragraph format should be standardized or use paragraphs with dot-point only for list based information. References need to be properly integrated into the page, instead of at the bottom of each section.

In the recent findings section 2 out of the 4 studies presented have any content. To improve cutting some of excess information for the 2 studies already addressed and creating summaries for the other 2 will create better scope of recent findings. The formatting of recent findings is unusual, proper placement of the “Hematoxylin/eosin” image”, removal of dot-point and removal of purple highlighting, will make the section easier for viewers to understand. Historical findings okay, more detail could be added to “skin”, “glands”, “nails”. Use of capital letters like “DEVELOPMENT” show be replaced with subheadings, the image “File:Screen Shot 2014-10-08 at 10.38.04 am.png” has not appeared properly, should be easy to fix.

Straight up the abnormalities section is amazing, no improvement needed. All 4 diseases have in-depth relevant information, sufficient referencing and images to allow viewers to visualise clinical manifestation. To improve use of dot-points or paragraphs should be standard throughout the project, referencing in beginning sections needs to compiled at ending of each Main heading or bottom of page, recent findings need 1-2 more studies, and recent findings need significant reformatting.

----

Overall I was very impressed with this project page. I loved your use of pictures and diagrams as it provided a great understanding of what was happening- and also, a lot of the images were quite interesting- which is a great thing for a project! I also enjoyed the use of bullet points- it was very to the point and it retained my attention throughout the piece. I did find, however, that the introduction was a bit short. Whilst it did cover most of what was required, I don’t think it hurts to be a bit more exhaustive in what you’re saying, because the introduction sets the mindset of the reader for the rest of the project- and if they have a clear understanding from the start, it makes it much easier when you are explaining more complex things such as the abnormalities later on.

Overall, I thought that the developmental timeline was extremely well done, and a highlight of your project. The rest of the developmental overview was quite well done, however I think in areas it was a bit sloppy, and it would be of great benefit to clear this up so as to improve the clarity of your work. Further, I enjoyed the succinctness of your paragraphs, it made it easy to read and wasn’t too much to take in at once. I think that currently, your use of colour is a bit random in the recent findings. I think that this could really boost your project if you applied it to more areas of the page. As far as the content goes, I think that the recent findings is just too wordy and I began to lose my concentration a bit. I think maybe by forming more succinct dot points- you will be able to convey your message more clearly.

I think the historic findings could do with a bit more beefing up, but what you have so far is well done. The abnormalities is also very well done, and I think that your use of images really grab the readers attention.

I think that overall this project is shaping up to be a great one. I think you need to be careful and consistent with your referencing though as I noticed some sections lacked in-text citations.

----

This page seems to be done extremely well. It looks very visually appealing as multiple images are used, information is presented in tables, bullet points and very few slabs of text. The introduction is short and to the point. You could possibly add to this area a tiny bit of info concerning the embryonic development of this system, where it first started, then mention how you will expand on the fetal development. Otherwise it just seems way too short.

Explanation of the organs in this system is well done and concise. In the glands section, I would suggest not using dot points for the function of the vernix caseosa as it looks as though the dot points continue from those of the glands, therefore can be confusing when first looked at. Other than that, I would suggest that you make sure your referencing is correct and is used within the text.

The recent findings area is nicely done, but I still can’t help but feel the amount of text is just too much, even though the section is made better looking by making it purple (keep the colour, it looks awesome). The slab of text is just too much, so you should try and simplify it a bit. Historic findings are few but there is at least one for every organ which is good (more would be better). The abnormalities covered are done well, going into detail and providing a good image to describe what it looks like. I would suggest having at least 5 abnormalities, one for each organ discussed.

Overall, this page is very well done, with lots of images and colour used. The main thing I would suggest would be to make sure correct referencing is used. There were some paragraphs were no references were used at all. Also, all references should be at the bottom of the page, not within individual sections.

----

This page has great overall structure and presentation. The introduction gives good insight of the overall contents of the page, however it is very brief and should be expanded upon.

The table included in the developmental overview serving, as a timeline is excellent, really well done. It’s easy to follow and looks very neat. I like how there is an image for each of the weeks mentioned, just don’t forget to add in-text citations for its contents. The glands sub-section is very brief and would benefit if there were more contents added. Great job on the images though. The nail section is the same, more contents needs to be added and image would look really good.

The developmental overview and historic findings sections also seems to lack in-text citations. There is also has an image with a broken link. The subsection hair seems to be well researched, however I would also suggest either bolding or underlining the words you want to emphasize such as “structure” for a neater look.

The recent findings section looks superb I love the purple background colour. Its very well researched and the link to more research papers are very helpful for readers. I would suggest you put the image at the bottom of the mentioned content though, just to avoid the big gap on the page, or even if you can manage to wrap the text around the image, it would look much better in terms of presentation.

Although disturbing, the abnormalities section I could not fault. Very well done. It is evident that it has been research well and the images allow for great visualization of the diseases mentioned.

Overall, excellent page just needs a very formatting edits and some expanded contents mentioned above. Good luck!

------

Integumentary
The introduction seems really over formal and non friendly. Maybe try rewording some parts to make it more reader-friendly and welcoming.
The developmental time line is absolutely BEAUTIFUL! It shows the week of development, a brief explanation of each, and a picture to visually explain what is happening! I think it’s the best developmental timeline of all the wiki pages! Awesome job :)
The references should be put together at the end of the wiki page before final submission.
Hair and nail sections are very well done, teeth section are in dot points; this should be converted into paragraphs to match the wiki page format.
The section on recent findings seem to be copy pasted? Or not yet converted into the students’ own words. The formatting is very different to the whole of the wiki page as well which should be changed. On the section on historic findings, you should try to find a picture to supplement the information you have.
The abnormalities section is very well done, pictures visually supplementing each of the abnormalities. The picture of the infant with harlequin ichthyosis especially helps the reader understand the degree of extremity of the abnormality.
Overall, very informative and well done!

----

This is a really well done project. You have made sure that that you have ticked all the boxes as well that Mark has asked for. The abnormalities section is really good. You have done well with most of your images as when you click on them there is a good description and they are well referenced. The development overview table is exceptional and makes the project easy to understand. For the week 22 maybe include the study in which you got your information from.

Apart from the abnormalities section it appears as though the referencing is a bit all over the place. Need to follow the abnormalities section and put references into the specific parts of the information you are using it for. Because otherwise it becomes difficult to know exactly where you got your information from. The historic findings are really good and well done however there is probably a space for more information to be included as I feel as though some of the findings are a bit hard to follow at times. It may have just been my computer I couldn’t see the picture of ‘fetal hair development’.

I think it would give a nice touch to the project if you were to add some student images because it would give the page a more ‘student’ and also make it easier to understand. Don’t mind the purple background on the ‘some recent findings’ part but it just looks a bit out of the blue. It’s certainly unique and attracts the eye but it puts a lot of emphasis on this section which I’m not entirely sure you want.

Overall though a really good project with excellent information. There needs to be a bit more focus on referencing technique, some minor edits which I have mentioned and maybe introduce some student pictures to make the project more student-like. Great work though and good luck in finishing it off.

--------

The introduction of this page was good as it provided a great overview and insight into what the project would later go on to discuss. Perhaps a little information on defining the integumentary system itself would be valuable though, to let the reader know the constituents.

The sub-sectioning of the page’s content into ‘introduction, ‘development overview’, ‘recent findings’, ‘historic findings’ and ‘abnormalities’ was clever, as the development section then went on to describe each component such as skin, nails etc. This effectively segmented the information into smaller chunks that could easily be navigated to. I especially liked the use of the table in the ‘skin’ section, showing the week of development, description and image corresponding alongside it, as it provided a holistic approach to that section. However, there were no in-text citations in the ‘skin’, ‘hair’, ‘nail’ or ‘teeth’ sections, hence the source of the information is unclear. To do this correctly, Dr Hill’s Wiki help page should be consulted.

The use of various images with labelled captions was a strength of this project, as the pictures were effective in balancing the text components to make the page more visually appealing. Most of the sections under ‘development overview’ have a decent amount of content, however the ‘nails’ part is a bit lacking and also needs to be correctly cited. The use of the table of images alongside the description of developmental stage in the ‘teeth’ section was very good to include, however the image is captioned ‘The stages of embryonic teeth development’. This may be irrelevant as the project’s focus is on fetal development. Further research into this area may uncover more relevant information.

Although the section on ‘recent findings’ contains a lot of information, the use of chunky paragraphs detracts from the readability of the page and the purple boxes could be summarised into dot points to help the reader understand the content more quickly. The section on historic findings seems concise and relevant, however the image included says it has been removed/deleted, so this requires editing. Lastly, the ‘abnormalities’ section was very well-structured and written, as each example had a captioned image accompanying it to help the reader visualise. This section was also well-done in terms of in-text citations, with an extensive reference list provided at the end. Perhaps consider adding some student-drawn images and possibly a relevant video, but otherwise it is very good as it is. Overall, the project has a good layout and a decent amount of content; with some editing and formatting it can be improved further.

----
Overall this is an impressive and well researched wiki page incorporating lots of pictures and tables to keep the reader engaged and interested. However there are a few areas that have the potential to be tweaked. Firstly there are references scattered throughout the page. A more attractive way of presenting the references is as a long list at the end of the page. The introduction is clear, concise and short. All the organ development section is well presented and has the right amount of information. It is well structured in the sense that the student introduces the organ, it’s embryonic origin, the fetal growth stage and then goes into slightly more depth in a bullet point form. Along with complementary pictures, this is a very effective way of presenting their topic. This page could be improved by adding student-drawn schematic diagrams to summarise the layers of the skin in particular since histological images can be confusing and unclear to a non-expert embryology student.

The skin development section appears to dwell on the content that was covered in lectures. Considering there appears to be only three references associated with the entire integumentary organ development section, the depth of the information is limited. By doing some more research you might be able to find interesting additional information that can be added. The recent findings section is interesting and the images are great. However the dense block of information and slightly odd formatting make it hard to follow. Perhaps using diagrams to explain the differing gene expression and breaking down the information into bullet points would make it more readable.

The historic findings and abnormalities section is particularly well done. The images complement the minimal yet important points made. I was left wanting to read more into it so that suggests there’s room for further development and a deeper explanation of skin abnormalities.

----

*Great overview given in the introduction. Maybe look to replacing the words "this page" to something else to avoid repetition
*I'm really liking how everything has been simplified into dot points and tables where relevant. Don't forget to include relevant references all throughout though, to justify all that you've included in each section
*I can't express how much I love your first table. Great work!
*Proofread so that you don't repeat the same things in your table though. You mention "in a study" numerous times but there's no indication to which studies they are
*I'm sure Mark would be thinking this same thing, but look to getting different references outside of this Embryology website, maybe from textbooks or otherwise for preliminary information on development
*The "recent findings" section looks nicely formatted but just a bit wordy. Maybe think of dividing the text up with bullet points or images
*Really liking your "historic findings" section! Great research
*Maybe think of re-creating some of the simpler pictures by drawing them yourselves. That way you're not using too many pictures from this Embryology website, Mark warned our group about this point
*Great choices for the "abnormalities" section. Traumatising at first, but very well-researched and presented

----

The presentation of this page is very well with multiple images being used and text organised into tables and dot points. The introduction is short however includes necessary information regarding what is being included in the project. I recommend adding background information on anatomy of the skin (explaining on different layers) and other structures as well as a brief summary on the embryonic development of the system so that fetal development can be further expanded throughout the project.

The development overview section is done very well and is divided into different sections each explaining the development of a different structure. The use of table, images and bullet points has made the page look very interesting. The table of the timeline in the ‘Development Overview’ is done very well and the use of histological images is excellent as it helps in visualising the anatomy at each stage. There is however no proper referencing, copyright information or student template for any of the images. The table under “teeth” is also a very good summary of events during fetal period. I recommend including self-drawn diagram as well, since this is the only feature missing from your project. You can include a drawing of the different layers of skin (possibly in the introduction section). I also suggest putting all the references under one reference list at the end of the page instead of having references at the end of each section.

The “some research finding” section is presented well with a different background colour to other sections (it is similar to recent findings in mark’s wiki pages). This makes the page look very visually appealing! You have elaborated on two out of four research papers which is very good. However I recommend describing the other two papers as well and even including more papers (It would be perfect if you could provide research papers for different structures). I like how the “more research papers” can be expanded for anyone interested.

Historic findings section is very well researched considering it is difficult to find information for this section. The ‘Abnormalities’ section is also perfect and complete with all four diseases having sufficient information and appropriate references. The images are also relevant and illustrate the clinical manifestations well. Overall this page is very well-organised and only minor issues mentioned above need to be fixed.

----
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

----

==Week 5==
Hey guys!! I found some research material that we can use to construct our time line!

Historic information is hard to find! I might go look at some text books in the library
--[[User:Z3418340|Z3418340]] ([[User talk:Z3418340|talk]]) 12:50, 27 August 2014 (EST)
How is everyone else going?

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 12:52, 27 August 2014 (EST) Hey!! That's great! I also found some material for abnormalities. There seem to be a lot about septal defects. I'm gonna try to look up for more defects.

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 22:53, 30 August 2014 (EST)Woo!! Nice to see more links in the page! Rehmina and I also thought that it would be easier for marking if one of the two people in current research do timeline instead because that would make marking easier and less confusing. But that's not final, it's only a suggestion. Also, Dr. Hill gave us some tips on what to focus/include in our research such as:
*Remodelling during the fetal period
*Changes during ossification - haematopoietic elocution from liver to bone marrow
*Early development of WBCs — hot topic right now!!

Hey everyone, yeah that sounds good with me.. :) so rather each person focuses on 1 of the 4 topics right? --[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:35, 31 August 2014 (EST)

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 18:36, 1 September 2014 (EST)Yep, exactly! I'm really glad that's alright with you but we can still talk about more in the lab.

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 12:14, 2 September 2014 (EST)Hey everyone! I just asked Dr. Hill about using review articles. He said it's alright to use review articles as long as you say that the information came from a review article when citing. We can also use images from review articles and there is no need to say that it came from a review article.

==Week 6==
--[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 20:19, 3 September 2014 (EST)Hey guys, I had a good talk with Mark today after the lab. Since we're doing the Cardiovascular system, it incorporates the (i) development of the heart, (ii) development of the blood vessels and (iii) the formation of red blood cells/white blood cells. But Mark said that as a group, we would be able to create and produce this web-site in a manner that we thought was appropriate. We could focus on one of the specific areas or more broadly on each area, if we chose to. But, MOST IMPORTANTLY, our project should be cohesive. What we talk about should be introduced well at the start and should be cohesive through out all of the subsections that we're working on. He really stressed the importance of us having a single, unified vision of our end product and that it should be succinct throughout it all. Im proposing that we actually decide what to focus on very soon.

: --[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 20:19, 3 September 2014 (EST) I'd particularly like to just focus on the development of the heart? Maybe incorporate the formation of blood cells if the research in the other areas is interesting and notable?

--[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 20:24, 3 September 2014 (EST)In regards to the use of the textbook, we are allowed to use the information from it if we cite it properly, but he really want us to be using articles (and even Review articles) to discuss our information.

I agree, the heart should remain our focus, but of course other aspects such as blood vessel formation/ blood cells would naturally fall into it as well- maybe just a brief mention wherever appropriate? --[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 21:22, 3 September 2014 (EST)

==Week 7==
--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 21:05, 8 September 2014 (EST) Hmm. I agree. Let's try and focus on the heart for now and see how we go? And if time permits, maybe we will be able to include the development of blood vessels and blood cells. Sorry I didn't reply so soon, kinda busy week for me haha!
: --[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 00:24, 10 September 2014 (EST)Ok that sounds really good and reasonable! I'd be happy to follow that plan. And yeah, same! Very busy week for me as well! But yeah, I think lets just focus and refine our research to just the development of the heart at the moment

--[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 00:40, 10 September 2014 (EST)Hey guys, Im having difficulty knowing whether the use of an article is fine or not?! If it says "Full-free-text" does that mean we're allowed to incoporate it? Because a lot of the copyright information, is very brief. Thanks heaps, if you guys know an answer haha
: --[[User:Z3418488|Z3418488]] ([[User talk:Z3418488|talk]]) 00:55, 10 September 2014 (EST)Ok, never mind.. I find out the answer haha. If it says "Open-Access" or "Full-free-text" it is only free to read online and may/may not be allowed for re-use. You'; have to read carefully or apply for permission lol. I guess i'll just be sticking to mainly the Public Library of Science (PLoS), Biomed central (BMC) and Springer Open... which we are pretty much able to use, with the right referencing and acknowledgement. I read this on the 'Copy rights' page on this wiki. http://php.med.unsw.edu.au/embryology/index.php?title=Help:Copyright_Tutorial. Can someone verify or correct me if i'm wrong haha?

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 11:56, 10 September 2014 (EST) I thought copyright only applied on images and not on content. It would be really difficult to write a report when the most papers have copyright. We can ask Dr. Hill in the lab just to confirm.

==Week 8==
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:56, 17 September 2014 (EST) Hey guys, so Carl and I had a talk with Dr. Hill and he has agreed to allow us to change topics from Cardio to Integumentary. To finalise the change all members have to personally email him saying we all agree to the topic change. Carl and I have started thinking about our approach to the topic and we think we should have a main focus on skin and smaller sub-topics on hair, nails, glands and teeth. Each members role just remains the same and any problems we will all still help eachother :)

==Week 9==
--[[User:Z3417796|Z3417796]] ([[User talk:Z3417796|talk]]) 12:46, 22 September 2014 (EST)Hey guys, I've added some headings for our new page just to get a start, we've got alot to catch up on, I guess we still have to talk about it as a group for the overall layout, we should all start adding some content soon.

--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 12:41, 23 September 2014 (EST) Thank you for fixing it! Yeah, we have a lot to do but that's okay. Midsem break is next week and hopefully we can get most of the bulk done before week 10.

==Midsem Break==
--[[User:Z3417843|Z3417843]] ([[User talk:Z3417843|talk]]) 23:24, 29 September 2014 (EST) Just wanted to let you guys know that Dr. Hill gave us some tips on what to look at a few weeks back. He mentioned "vernix caseosa and fetal hair." Here's a wikipedia link to vernix caseosa (http://en.wikipedia.org/wiki/Vernix_caseosa) just to give you guys an idea on what it is. I'm aiming to finish before the end of the week so that I could help anyone with their parts. Anyway, I hope everyone's having a good break!

Talk:2014 Group Project 4

2014-10-14T15:59:47Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

The Introduction, Current Models and Current Research section all in dot-point form, which obviously allowed you to more easily, put information on the page. These need to be converted into paragraph form to give the content greater readability and flow.

Presuming the system development is supposed to be the introduction, there should be inclusion of current research, historical research and abnormalities. Without these the reader will not know all the sections of the page after reading the introductory section, which is the intros purpose. The use of bold and capital letters is unneeded. The existence of a table is good though has a bunch of formatting and text problems (capitals, bold, captions, lack of lines). “(around week 4-6) that sexual differentiation occurs in the fetus ” this statement is incorrect since it is an embryo during the week4-6, it becomes a later around week 10. “450px” has not been inserted properly, the sexual differentiation image requires caption and references.

Current Research and Models has in-depth content for undifferentiated and male, though limited information on current female genital research. The headings are repetitive also many without any content, similar content needs to be merged under single headings. In Historic findings the content and wording is good but same trend continues significantly more text on Male development compared to female.

Abnormalities section is great with even attention given to female, male and both. Information is appropriately in-depth and referenced, addressing causes, process and treatment. Addition of 1-2 images in the “both” section is advised, to allow readers to identify clinical features of the diseases. Like the use of drawings especially “Abnormalities of the Uterus and Vagina” and “Anat of Testes”, you should change the caption of the testes drawing from “alt text”.

For improvement; covert of dot-points into paragraphs, expand on female sections of “current research” and “historical research”, fix a few image problems and remove unnecessary bold/capitals/captions.

----
A great start on tabulating the information about the development of this system. There are references but I don’t see any in-text citations. The image used in this section is really good and relevant. It clearly shows the major processes in the development of the genital system. However, it is a bit pixelated so maybe try resizing the image to a smaller size. Maybe try uploading the image again with a different filename, change it to something more appropriate rather than “Image.jpg”. And also, if possible, try to include it in the table. Good job on embedding a video! I think this is the only group so far that has included a video. It’s a good video about the development, I just wish it had a voice-over explaining what is happening but that’s not really the group’s fault. Nonetheless, great job on the development section.

With the current research section, great use of dot points but a bit excessive. Maybe try to make paragraphs where it is appropriate. It is well-researched, very detailed and very informative. It’s good to see student drawings. Great job on that. I see that an image was not properly uploaded into the page, so just fix that. Good job on referencing. All research articles seem to be relevant to this section but try to incorporate some of the in-text citations of the remaining articles, not just the first three. Overall, really great job on the content of this section. It is evident that the person responsible for this section put a lot of effort in research.

As for historic findings, great job! I know this is probably the hardest of all the four sections in terms of finding information and this section is well-researched, very detailed, and very informative much like the current research section. Maybe try to use some dot points to lessen the bulk of this section. Great drawing included in this section. Try to add more, especially for the males since that is the bulk of this section.

Lastly, for abnormalities, great job on finding lots of abnormalities! Lots of references and each area of this section seems to be well-cited. The content of this section is very concise. All the important information about the disease is included, from the cause to the treatment. Good work! Try to find more images for the other abnormalities. It may be tedious but it will help in visualising the clinical manifestations of each disease. Overall, this group has done their research and did it well. Great job on the table for development and images. Their page is very clean and very organised, particularly the references. Don’t forget to write an introduction for your project’s page.

----
Just looking at the contents, if feels a little intimidating both in that it is so long as well as the use of caps. You should try and limit both; the use of all caps can be quite annoying in text and the extensive contents list can make people dread reading through your page if it looks like it’s quite long.

An introduction is recommended as it is usually a good starting point to provide the reader as sense of everything the page will cover. The system development is a little messy, but I will heed your note and pay attention to only the table. The table itself is a great idea to lay out all the events happening in the corresponding weeks, making it look neat and concise. However, the use of all caps, bold text, and two different fonts still makes this section look messy. Having both male and female events on the same table makes it look as if there is a chunk of info missing for the female side as well. I would suggest having them in separate tables next to each other, which would eliminate the empty rows in both areas. Both the image and the video (congrats on finding a video! Really good addition to the page) should be captioned.

The current research, models and findings seems well researched as there are a lot of points made. However, it is all presented in bullet points which can be visually unappealing. Some sections look incomplete as well, so an effort needs to be made to finish these areas as well as present them in an appealing manner e.g. in paragraph form with a picture next to it to both describe the text visually and offset the amount of text. The drawing of the testes should be captioned appropriately instead of the ‘alt text’ provided. It should also be enlarged, as its current size isn’t large enough to view any of the labels properly.

Historic findings looks well researched on first glance, but then I saw that only 4 sources were used to reference the section. It looks really bad when only one source is used to reference a large slab of text, which you have done twice. I suggest finding articles that state similar information and using them as references as well, to back up your current information found. Other than that, I suggest possibly formatting your section in a more appealing way; either summarize some areas in dot points, and add a picture.

The abnormalities section is nice and concise, without going into too much detail which is good. Just make sure you explain what it is, how it is formed/how you get it, some statistics and possibly an image to show what it looks like, and that’s all I believe you really need for this section.

Overall, your page is well researched with lots of info. Just make sure it looks visually appealing, is consistent in terms of font and presentation, images are used and captioned correctly, and all references are placed at the bottom of the page.

----

Firstly, great job on all the contents you guys managed to present, it’s quite detailed. There seems to be no introduction though, and the page jumps straight into explaining genital development. I think if an introduction were added, it would give the whole page better structure and formatting so the reader knows what to expect when they decide if they want to read on. The dot points used for the developmental section allows for easy readability of the contents, however, the use of caps lock and arrows takes away from the overall presentation of the page. I would suggest any text you want to emphasize to make bold or underline the word. I also noticed that there was a note stating the attempt to put all the developmental information into a table, but had issues. I suggest you look at the editing basic page you can search for in the top right hand corner as it outlines a step-by-step guide into making tables etc.

In regards to referencing, there are no in-text citations for the first two subheadings. The sections were they do have citations also have a list of references at the bottom of each section. I would recommend just adding a final list of references at the bottom of the page, as it looks much neater.

I’m impressed with the level of hand-drawn diagrams uploaded. I would also recommend adding captions to the image. For example:
[[File: Flow Diagram of Fetal Development of External Genitalia.pptx|1000px|thumb|right|alt text]]. The “alt text” should be edited to describe the caption of the drawing. This particular image seems to have a broken link though; the “alt text” also appeared in the labeled diagram of the testes. Otherwise, good job on the other images.

The current findings section seems to be untouched, with the exception of some pubmed journal article links, I’m assuming you are still in the process of adding content. The historic findings, however, is extensive and well researched. Good job.

The abnormalities section is done well. There is more than enough abnormalities listed, and they are researched well, I would just suggest adding a few more images for better visualization. Overall, great page, just needs better formatting for the mentioned sections.

----
This project would benefit from having an introduction to prepare the reader for what is to come and summarise everything briefly. The system development part is interesting and clearly there has been a lot of research put into finding the information. I suggest adding pictures or student-drawn diagrams, particularly of the chromosome and the SRY gene location to make it more comprehendible. If you’re not a geneticist, it can be difficult to picture that much detail at an embryonic level.

It is clear you have considered inserting images so it would be important to follow through with that before the final stages of marking. I’m not really sure why you’ve inserted a table here as well since a lot of the information was already covered previously. Maybe use less information in the table. The references at the end of this section should appear at the very end of the wiki page. A lot of other groups have already done that so if you need to copy the formatting, it’s definitely possible. The use of a video on your page is commendable and sets this project above others in that sense. It’s a great idea to have a youtube clip. However, it is 9 minutes long which is a bit long for a student page that is designed to inform students on the genital system on a wholistic scale rather than tackling complicated ideas. Maybe try editing the youtube video so you only use a 30 second or 1minute clip.

The male and female genital development section is clearly presented and the use of bullet points make it easy to follow. However reading the information, it appears that a lot of it I recognised from the lectures. This doesn’t suggest the student explored external embryology sources. On another note, perhaps the lecture on the genital system was very indepth and this student did do research but found all the relevant information had already been covered. None the less, I think it would be advantageous to add a subheading in the section that looks at recent findings. This would broaden the understanding an embryology student can achieve by reading this wiki-page. Also there has been an error uploading an image so that should be fixed.

Although the information is presented well, the bulk of references should be included at the very end of the page. This project is very good but there is still some further research needed, particularly under the current findings subheading. The information presented under the historical findings subheading is quite dense and would benefit from being broken up into a table or simple bullet points. The abnormalities part is excellent and there has clearly been broad research into different embryological resources.

----

Overall, it is evident that a lot of work has been completed on this project as each section has a decent amount of information and there are images throughout the page. However, the addition of an ‘introduction’ section would help to orient the reader and help students gain an overall understanding of the topic.

The section on ‘system development’ seems to be well-researched, however the formatting of the content in short, one-sentence dot points makes it difficult to read and incongruent, so writing this out in small paragraphs would improve the readability. The capitalization of some words is unnecessary in both the dot points and the table, creating inconsistencies in the formatting. Also, some words are unnecessarily bolded which detracts from the aesthetic appeal of the page. However, the inclusion of a table to summarise the timeline information is an effective tool, although there is much more information provided for the male system than female system. It is really good to see the use of an image as it is relevant and clearly compares the male and female system development side-by side. I also think the video inclusion is fantastic as it would be an effective way to learn for a reader with no previous knowledge, making the page more interactive.

The section on ‘current research, models and findings’ contains lots of relevant information, however this is not referenced in-text and it is thus unclear where the information has been derived from. There also seems to be some unevenness between the depth of information between male and female systems, which some more research can easily remedy. In terms of current findings, the listing of the information in dot points makes it easier to read, however there are some parts italicised and capitalized that are not needed. It is great to see some hand-drawn images as these are simplistic, colourful and effective ways to accompany the text, adding to the page’s appeal. Take care to properly include images, as one of them appears as ‘alt text’ and the link does not show the image itself. Although some references appear under a ‘references’ title in this section others appear as a website links; formatting of these could improve neatness.

The following section on ‘historic findings’ contains evidence of extensive research as it is very detailed and well-written. However, I would consider breaking this part up into smaller sections using dot points as large paragraphs seem tedious to read. The hand-drawn image is a good inclusion, but labelling of it would be effective and adding a couple more would break up the long section visually. Also, there seem to only be in-text citations after long chunks of information; perhaps more sources should be used/consulted.

Lastly, the abnormalities section was comprehensive and detailed and enough information was given on some examples. This was just the right amount of content, as any more would seem excessive. Adding some more images with appropriate captioning is advised also. I liked that the references were listed altogether at the end of the page, making it neat and tidy. Overall, a solid project which just needs some formatting to improve further.

----

Don’t forget to add an introduction which clearly lists the outcomes that the page hopes to achieve!

The table in the development section is excellent and very clear and informative. I believe you could summarise the text above and add it to table to improve the presentation. There is a very good choice of categories and headings/subheadings. The information presented is excellent. Remember to just correctly cite the information and improve the overall format of this section.

There is an excellent choice of headings and subheadings in the current research section. It is very informative and demonstrates significant scientific research. I do believe that this section could be summarised or the presentation improved? It is a bit wordy- try to summarise more or present the information in paragraphs/a table? (only a suggestion though). The addition of hand-drawn diagrams was excellent and very admirable

The historic findings section was excellent. There was a very good choice of headings/subheadings. The information provided was very informative and demonstrated significant scientific research. However, it is a bit wordy and would be benefited with summarising the content further. Though the content has been referenced correctly, I believe it could be further enhanced with more references to verify the possible points. The addition of pictures would also benefit. Excellent work nevertheless. Very informative section

The abnormalities section was excellent. A very good choice of headings/subheadings and a good variation of abnormalities included. It was referenced and cited correctly. Demonstrated strong scientific research. Maybe improve this section with the addition of more images? Nevertheless, an excellent, clear and informative section.

----

Genital

There is a lot of information with hardly any pictures or diagrams to support the information. It is currently very not appealing visually.
System developments, Current research, and models and findings are all written in dot point form which should be converted in paragraph format before final submission to match the wiki format. I think that you should add an introductory section to tell the readers what the genital system is about, and what its function is in the adult. Also you should definitely put the references together before the final submission date.

The historic finding section is very detailed and well explained; it’s very well done. The abnormalities section was very well done and easy to understand with no punctuation errors etc; the drawing of the uterus/vaginal abnormalities were very easy to understand and self explanatory. I found it really nice that the abnormalities section was further divided up into female / male and those which both genders can have.

As for points to improvement, flow of information and it’s formatting can be improved by moving subheadings to more appropriate places, and also by labelling the pictures and diagrams.The contents at the start of the page is very well sectioned. I love the video; your group wiki page is the only one with a video, and it’s really informative and helpful, especially for visual learners like myself.
Overall: VERY well researched and detailed!!

----

In this review I will attempt to highlight the merits of your project and provide some constructive criticisms in light of the marking criteria.

Great work on system development, a lot of research has been done and the page seems well organised. I suggest using the information you have collected to write up succinct paragraphs, with forget in-text referencing. Furthermore, I find that that the table is a really effective means of summarising everything, you’ve made good progress so far. I also feel that the diagrams and video really support the text and have been appropriately selected.
The current research section is a looking good, it’s great that you are exploring the molecular signals driving genital development, with references to FGFs, SHH and BMPs. I think this area needs to be addressed in further depthg. I also suggest including relevant studies, methods and findings. Finally don’t forget to include references!

I see that a significant amount of research has been conducted on the historical understanding of genital system development. Your project provides a particularly interesting insight into the debate on mechanisms of testicular decent. To make this section more interactive and engaging I would suggest the inclusion of historic illustrations and diagrams. There are many images available on both the UNSW embryology database and the UNSW library database. I also suggest that further research of the female genital system. Finally use in text referencing to support your data.

The section final section of your project investigates a number of male and female genital abnormalities. The diagram on abnormalities of the vagina and uterus is particularly interesting and certainly assists my understanding of these abnormalities. I simply suggest that you provide a little more depth on each abnormality. Ensure that you address the following areas are addressed: Cause; Description; Treatments.
The page is well structured and incredibly cohesive. The references are well organised. Finally I’m really impressed by the drawing and diagrams. Great work so far! Just make sure you include that introduction in the end and add all the diagrams and images you plan to.

----

An introduction is recommended as it is usually a good starting point. I suggest starting by giving background information on the anatomy of male and female genital systems. You can then talk about the embryonic period and give a brief summary of how this period is different to fetal period. You can then briefly mention the significant events that occur during fetal period and the sections you are including in your project (including abnormalities and research findings).

The table in the system development is a good summary however it looks a bit messy at this stage. I suggest having two different tables for male and female, avoid using all capital letters and bold texts in the table. I also suggest starting the development section with a brief paragraph on early stages of development. The image included under ‘system development” is a very good summary but it needs to be captioned and referenced. I also recommend re-uploading the image in a smaller size to improve the quality. The use of the video is also very creative. Well done for finding this helpful video!! It would be perfect if you could reference the video and maybe include a few sentences on what it is showing. Overall, the development section is very good with the use of different methods to help in learning. To make this section perfect, you can add some details in paragraphs to explain more on different stages of development.

There is a lot of information under “current models” which shows extensive research, however I find this section hard to follow. Using paragraphs instead of dot points will result in a more coherent flow. Also the studies need to be referenced appropriately; it would be a good idea to include the name and year of the article in the text. The division into “current research” and “current models” is a smart thing to do however in both sections the amount of information provided for male is much more than female therefore more research needs to be done for female. I like how a self-drawn image is used; it would be a good idea to include a description for the image (rather than “alt text”). Also make sure that all the references are listed at the end under one reference subheading instead of having different references for each section. Also, great job for historic findings! This is the most difficult section but you have managed to include detailed information. Similar to current research section however, most of the information found is for the development of male system. Try to add to historic findings on female system if possible.

Abnormalities section includes a significant number of abnormalities with causes and treatment of each abnormality addressed precisely. I also like how you divided this section into female, male and both. Information is well referenced and helpful images are included. Make sure that your images are referenced. If self-drawn images are used, then you can briefly mention that in your text. I would also recommend adding more images for other diseases to illustrate the clinical manifestations of each disease. Overall this group has done an extensive research and the methods used (such as drawings and videos) are very creative and helpful. Well done!

----
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

----

==Group Topic==

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 14:08, 18 August 2014 (EST)
Hi everyone :),
We all need to decide on a system for our group asap, does anyone have any suggestions ? I was thinking we could do the Genital or Musculoskeletal ?

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 17:45, 19 August 2014 (EST)
Hello, I was thinking of covering the genital system development as well.

--[[User:Z3417753|Z3417753]] ([[User talk:Z3417753|talk]]) 20:39, 19 August 2014 (EST)
Genital it is :)

--[[User:Z3416697|Z3416697]] ([[User talk:Z3416697|talk]]) 11:07, 20 August 2014 (EST)
Great can't wait! there seems to be a lot of info about genital embryogenesis

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:07, 26 August 2014 (EST) Hey everyone, just wanted to make a note of what each of us was going to research. So as we all discussed last week, I am happy to do part 5. Abnormalities :)

--[[User:Z3417753|Z3417753]] ([[User talk:Z3417753|talk]]) 23:18, 26 August 2014 (EST) Hey ! Yes im doing current research models and findings :)

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 01:05, 27 August 2014 (EST) Thank you all for referencing your articles. I am having some difficulty with referencing 1 of my 3 articles mainly because they are not from Pubmed. I will consult with Mark tomorrow and have my part completely uploaded during the lab. Thanks for your understanding.

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 14:57, 1 September 2014 (EST) Hey All, just wanted to let you know that there are some really good pictures showing the differentiation between the male and female genital development in the textbooks. So maybe this week we could decide which ones we like and then I can try to draw them. :)

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 17:27, 2 September 2014 (EST) That sounds really good. If we are not given some time tomorrow during the lab to meet with our group and if you all don't mind we can stay back for 10 minutes or so to have a look at the images you found and if anyone has found any interesting material. See you all tomorrow in the lab.

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 18:06, 9 September 2014 (EST) Hi, I know we can only use one image from wikipedia so maybe we could use this one ? Or has anyone found any others ? Heres the link -- > http://en.wikipedia.org/wiki/Sexual_differentiation#mediaviewer/File:2915_Sexual_Differentation-02.jpg

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 18:14, 16 September 2014 (EST) Hi everyone, I am going to post 2 images on here tonight, please let me know which you prefer :)

1. [[File:Image.jpg|350px]]

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:04, 16 September 2014 (EST) Or this one ->

2. [[File:Sexual Differentiation.jpg|350px]]

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 14:42, 21 September 2014 (EST) Since my part is historical findings, I have found a few old articles around 50-100+ years old. Below I'm going to past a paragraph about the female genital system development I have composed from information of two articles, one is from the 1950s and the other is 1890s. My only concern is what I have written doubles up with the system development part of this assignment so I have not uploaded onto the page but if you guys think it's fine for historical finding then I will, if not we can add that into system development and the timeline. I am still searching for historical teachings and images that can be used in this assignment.

The mullerian (paramesonephric) ducts, found laterally to the wolffian ducts, are the original structures of the female reproductive system. Female sexual organs (the fallopian tubes, uterus and vagina) originate from the mullerian ducts, which differentiates within the foetal developmental phase. Initially the foetus contains two mullerian ducts, however by the ninth week fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, however the these two organs are not continuous with vagina being solid. The non-fused upper part of the ducts emerge into the fallopian tubes. It is not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month, between the continuous vagina and uterus. Also within the same month, the formation of the hymen occurs. The hymen is described as a pouting vertical slit and represents the remains of the mullerian eminence

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:05, 22 September 2014 (EST) I think it can be added under your heading of historical findings :)

--[[User:Z3417753|Z3417753]] ([[User talk:Z3417753|talk]]) 12:26, 1 October 2014 (EST) hey guys hope you are all enjoying your break :) Hope your assignments are all going well :)

Also, I found this article that might be useful if you havent already found it - it goes under historic findings - it is from 1942!!

Schonfeld WABeebe GW Normal growth and variation in the male genitalia from birth to maturity. J Urol 1942;8759- 777

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:59, 2 October 2014 (EST) Hey, hope your enjoying your break too. Thats great :). If you any of you guys come across an image that we could use for the first page, post in on here so we can decide if we want to use it. :)

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 16:16, 5 October 2014 (EST) Thank you, I'm doing the historical findings and I will have a look into that article. Thanks again. I have just redrawn an image from one of my articles about the Mullerian ducts and forming the female genital system. I will try and upload it following the steps Mark gave to us in the first lab so once it is up please let me know if you guys like it or not. Thanks

--[[User:Z3415716|Z3415716]] ([[User talk:Z3415716|talk]]) 16:57, 5 October 2014 (EST) Also another thing, please let me know if I am being too specific in my part (Historical findings). I still have more to add on other areas of genital development, so if what I am doing is fine then I will continue this way, if not please let me know so I can change what I have. Thanks again.

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 16:15, 6 October 2014 (EST) Hey Everyone, I've found a video we could use on our page, the background music is a bit annoying but the drawings are really good, detailed and clear heres a link. Let me know if any of you have found some too. :)
https://www.youtube.com/watch?v=MureNA-RSZM

----

*Great progress on the table. Maybe once you've managed to format everything you need into it, don't forget to reference bits you need to
*I liked the diagram you used to show the different pathways of genital development for the different genders. It's just a bit blurry so maybe think of re-uploading a clearer image or of making the image on your page a little smaller
*Good use of dot points under the "current research" section but maybe think of connecting the separate points a bit more as it seems a bit disjointed and difficult to follow. Maybe think of having your write-up as normal and using points in particular parts that show a sequence of events, or separate components of something
*Look to getting more references for the current research and models section because you're just using 1 at the moment
*Proofread. I know maybe you guys are still at the collation of information stage, but I find it's easier to get it right as you go along rather than coming back to it later
*Re-phrase some bits like: female and male fetuses’ external genitalia --> The external genitalia of the female and male fetus
*Great drawn images! They're all so clear, well thought out and identify all relevant components of what you're trying to show all throughout your page
*I liked the detail of your "historical findings" section

User:Z3333429

2014-10-14T15:59:09Z

Z3333429: /* Gastrointestinal Group */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

Talk:2014 Group Project 3

2014-10-14T15:58:30Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

‘GIT system overview’ section is good but requires more information to introduce the GIT and what the page is going to have information on. Timeline could form part of this section and could also preferable be in the form of a student drawn image or even a table. The overview section also contains no in-text citations. It’s a great idea to split the GIT into the three parts: foregut, midgut and hindgut to aid in understanding. There is not much information on recent findings without any mention of current models as well so perhaps it would be best to address this before final submission.

In the foregut section there is not much mention of blood supply or innervation as was done for midgut and hindgut. Student drawn images are very impressive and referenced correctly with the student template, description, title and copyright information. The features of the midgut section could include some histological drawings or images. The ‘abnormalities’ section does not contain many in-text citations in one of the paragraphs and could include more deformities listed and described with more images, as well as information on how to treat and manage such disorders later in life. There is also no information or images addressing historical findings or current models so this needs to be looked into.

The references are correctly done and ordered, and are present at the bottom of the page. Some of the in-text citations aren’t throughout the text like they should be, for example, in the stomach, liver and gallbladder, and oesophagus sections.

Overall, good effort so far but more extensive research needs to be conducted for models and findings and more information for Abnormalities, as well as a few minor edits to make the page present more nicely.

-----

Good introduction, initial description of fore/mid/hindgut with listing of respective structures gives the reader an anatomical starting point. Fetal development is presented in appropriate depth. There is no acknowledgement of embryonic origin, research or abnormalities. These sections should feature in the introduction to present all parts of the report in the intro. The three separate timelines defeat the purpose of a timeline. These should either be merged into a single large timeline and remain at their present location or moved to introduce the foregut/midget/hindgut sections later on. Recent findings has a single study which is covered in good detail though 2-3 more studies would allow the reader to further understand current GIT Research.

In foregut section the dot-points used should match your subheadings. For example duodenum development is covered in the stomach section but is not mentioned in the subheading resulting in its development being hard to find without trawling through the text or “Ctrl-f”. Additionally you seemed to have missed out on pancreas development entirely. Foregut could also use some more images 2-3 would be suffice. Midgut development has great information, strong table, 8/8 drawings(captions required though). Inclusion of histological features gives viewer a microscopic perspective on development. Hindgut cloaca partitioning content is well worded though references are lacking.

Anorectal deformities sections should be moved under the Deformities section. The type of dot-point style used should be standardized. Too few abnormalities in the deformities section, though after the hindgut deformities are mover there should be sufficient. There are no references supporting the possible causes of Gastroschisis. The referencing it very good unlike other pages there are no random reference subheadings. In overview format wise quite attractive, information is adequately in-depth in all sections, introduction fails to address whole page, referencing is great for a draft (exceptions being “introduction” “Liver, Gallbladder and Bile Duct”), some captions aren't present, abnormalities in development section should be moved into deformities/abnormalities section.

-----
The introduction is good as it accurately describes what the GIT system is about and the anatomical positions of the features in this system. It also briefly highlights the development stages at embryonic and fetal stages, however ‘embryonic development’ should be mentioned in a little more detail to understand how far in development the fetal stage begins. I also think the introduction should include a sentence or two describing how abnormalities in such organs can lead to these diseases. Basically a bit from each major subheading should be incorporated including current research as an introduction is a summary of the whole page. As for the ‘timeline’, it would’ve been more appropriate to place the timelines under each section, e.g foregut timeline under the ‘foregut’ subheading. This is because viewers would be confused on why there is so much difference in development in one section of the page. A glossary list should be incorporated in a separate subheading to define some of these words such as hematopoiesis so that viewers can fully grasp the information.

The information under recent findings is quite interesting and relatable to the content which is GIT fetal development. However, I believe more findings could be incorporated under this subheading. The information under each organ of the three ‘guts’ are quite detailed in fetal development which is good and shouldn’t be too difficult for the viewers to understand. However, I believe the group could include information on the function of these organs as well. The structure of the information under ‘guts’ does not flow in the sense that the midgut includes features and structure whereas the other ‘guts’ do not. The innvervation and bloody supply of the hindgut should be incorporated in a paragraph instead of being listed like that. All the deformities should be places under one subheading to make it easier for viewers to navigate. The abnormalities were also concise and related to the topic. Overall, the content is relating to the topic of the project and addresses key points. It also shows good amount of research, however there seems to be too much information in some parts which could be reduced a bit. The project needs a coherent flow of the structure.

As for images, there needs to be an image under introduction which includes all features of the GIT tract. There are a lot of potential images missing under each subheading except for the ‘midgut’ section. This shows that there has been one person working on this section or one section being focused on in comparison the others. The information used to reference the images is missing in some images such as the ‘Human- fetal week 10 sagittal plane D.jpg’ (although this is uploaded from a different user so this is understandable. However images such a ‘GIT 2.jpg’ need more information including ‘student template’ as well as the reference where the image idea may have come from. Also, if this is a hand-drawn image then please state this as one member did in ‘Week 11 midgut herniation.png’. Overall, I enjoy the use of self-drawn images as it makes it easier to show what the content is saying without going through the stress of looking for an image online that doesn’t relate to the content. However more images definitely need to be added. The use of footnotes is also good and indicates what the images are showing.

There are sections where incite referencing are used, however some sections are void of them such as the ‘introduction’ and ‘Liver, Gallbladder and Bile Duct’ (the [6],[7] should be placed next to the text not above the text. The use of a ‘references’ subheading is good the same references have been combined into one number showing that the group knows how to make the references set out. The use of a table in formatting the ‘Percentage of Foetuses Herniated’ is great and shows more that the group has done research. Overall, this is a good project and if the group makes edits based on the peer-reviews received, this could enhance their project.

-----
A good introduction to the page but only outlines the developmental part of the project. Don’t forget to include other sections as well like current findings, abnormalities, etc. Also, no need for the hyphen for foregut, midgut, and hindgut. The development timeline is really good. Its very concise and well-referenced. It could be improved by tabulating the whole thing and maybe try to fuse the three sections together. Also, add an image or drawing of the development of the system. It will definitely help in terms of understanding what is happening at each stage. On recent findings, it’s not as good as the other groups but it’s definitely a start. Most groups write about 2-4 research articles for their current findings sections. As for the development section, each section is very detailed and informative. Maybe add a few images for the foregut section because images are really helpful. As for midgut, great to see images and student drawings. Good job on that. The same can be said for the hindgut section. It’s written well but maybe put the deformities in this section with the “Deformities” section. Deformities (abnormalities) section is good. It is detailed and the image used clearly shows what the disease is like. Maybe writing about 1-2 more abnormalities would make this section better.

It terms of citation and referencing, midgut section did the best job. I recommend the other sections to look for a lot more related material. I understand that this topic was divided depending on the region of the GIT, particularly the development section, but make sure to reorganise each section to make the page coherent. As for the images, most of them are well referenced. It wouldn’t hurt to add a few more. It’s great to see a lot of student drawings. Overall, a good project page very detailed in most areas but very little in referencing. In summary, focus on adding more references, making the whole page coherent, and a few more on the abnormalities.

----
The introduction provides a good basic outline of the overview of the GIT. Although, there are no in-text citations in the introduction and all sub-headings are not included into the overview. Be wary of spelling errors such as “GIT (Gastrointestinal Track) consist of the Fore-gut, Mid-gut and Hind-gut” that should read Gastrointestinal Tract consists of the foregut, midgut and hindgut. This section would be better it was expanded upon and images were added. The timeline provides good detail, though would benefit by better formatting and organisation of the information, maybe putting it all into a table, by week will tidy it up.

Adding images for the sections will definitely be beneficial. The images hand-drawn are great, although the colours used make it hard to read. If you plan to add anymore drawings, try and use dark colours that allow for easy readability. The images already uploaded are missing copyright, referencing and “student template” information for images such as “fetal week 10 sagittal plane”. I would suggest you look up the tutorial for uploading images on the pages as Mark has extensive information for the proper steps required for uploading images.

The deformities section should be re-titled abnormalities as per the assessment criteria and would ensure the group is following similar structure from the other projects. Again, adding an image per disease would be great. Try and do about 1-2 more abnormalities. Great job on putting all the references at the bottom of the page, it makes it very neat and accessible. Overall, a good project just needs a few edits.

----
A good overview of the GIT, very descriptive. This section would need some referencing as most of this info isn’t exactly common knowledge. Some of the sentences seem too short for me e.g. I would reconfigure the third sentence and combine the fourth and fifth sentences into one: ‘The GIT (gastrointestinal tract) consists of three regions: the foregut, midgut and the hindgut. The majority of the organs are located in the foregut, including…..’. You also need to make sure not to use capital letters in the middle of sentences.

The timeline is sort of well organized; it’s good that you have it separated for each region so they’re not all muddled up together, but is the info in dot points under the week, or is it just written next to the week? It needs to be kept consistent. I feel like this section is a bit too spread out as well, a large portion of the left hand side has text, while the entire right side of the screen is empty. You could possible put in a picture showing these 3 regions of the gut to fill in the space? Or maybe format the info into a table, it would make it look more formal and structured. The proper referencing technique should also be used here, not added hyperlinks.

The recent findings area is a little sparse, so you should try to find a few more. The title does say findings (plural), so maybe add at least one more. The foregut section is very extensive on the information provided which is good, a lot of research has been made. Visually however, it looks a little bad as all that can be seen is a mass of text. This can be alleviated if the same thing is done as has been with the midgut and hindgut region: the use of bullet points, a small table and the use of images to offset the slabs of text. It makes it more visually appealing. Unlike the midgut portion of the page, if the images are hand drawn, make sure they are clear, legible, and with colours used that will not strain the eye. For the images drawn in that section are messy and the labels hard to read both due to the colour of the pen used and the handwriting. In both the foregut and hindgut, referencing needs to be done. There are slabs of text in both sections where no references are made.

The deformities section is good, kept simple with no extensive explanations. Are there only 2 possible deformaties? If so, might be good to write a sentence mentioning that. If not, would be good to have at least 2 more deformities listed. The image drawn in this section is very neat, I like it a lot. The only problem with it is that it’s too small, making it hard to read some of the labels.

Overall, I think this page is very well done in terms of content. You have a lot of text, but I think it could do with some more pictures especially to offset some of the large slabs of texts in some areas. Make sure the pictures you have a clear and neat, and make sure you are referencing and doing it correctly.

----

Overall this is a good project; I enjoyed the tailored diagrams and presentation of information in a succinct manner. Information is presented in a logical and coherent manner. The presentation of information into specific components such as foregut, mid gut, hind- gut is great.

The quality of research is exceptional and well presented. Specifically, the subsection of mid gut and the use of visual aids assist immensely in the translation of complex concepts into simple ones. The use of dot-points succeeds in summarizing the information into easily digestible sections. This also improves the clarity of the page. The use of subheadings also assists with the logical analysis of the project.

However, the referencing could potentially be more extensive. A further expansion on current research model and findings will prove to be instrumental in generation of a solid understanding of the project hand. I would recommend splitting recent findings into current research models and historic findings.

It would have been beneficial to see more information on the foregut section, as this would have provided a pronounced understanding of the topic at hand. It would assist in the comprehension of the data if the timeline were tabulated. Further expansion of the abnormalities would be needed. It would be great if the abnormalities in the hindgut were moved into the abnormal section. The grammar and punctuation is sound and the readability is good. The presentation of information is lucid and shows a sound understanding of the concepts involved.

----

The introduction part of this project provided a good overview of the gastrointestinal tract and its components, also mentioning briefly the changes that occur in the fetal period. However, care must be taken to not capitalise words that are not needed e.g. Foregut, Midgut, Appendix etc. Although the information in the ‘timeline’ section is relevant, its formatting needs a bit of review as there are inconsistencies between the foregut, midgut and hindgut parts. It also seems that the in-text citations have just been arbitrarily placed in chronological order, with each line having a new reference. Also, this information may be better presented in table format to improve readability. Some simple editing may be needed to fix this.

The section on ‘Recent findings’ has some good information, however the reference needs to be properly cited and maybe a couple more articles would help give this part some substance. I thought it was effective to have the GIT split into the foregut, midgut and hindgut and then detail the fetal development under those titles. This gave the page a good structure. However, adding some images, both from online and student-drawn to the foregut and hindgut sections would help improve the aesthetics of the page. The hand-drawn images on the midgut section are effective learning tools to a student, but maybe could be drawn a little neater with darker colours as the blue labelling is difficult to read. They should also be captioned. The use of a table to show midgut herniation of fetuses was a good tool as it makes the information easier to read also.

Lastly, the section on abnormalities was well-detailed and I liked that the deformities were split into a definition and cause. An image of gastrochisis may be helpful for a reader to visualise the condition though. The in-text citations in this part were properly done and a long list of references being at the end of the page made the project look neat overall. Areas of improvement may be some simple formatting changes and evening out the information across sections, however a solid project so far.

----

Gastrointestinal

In the overview section, the words “GIT” suddenly are used without any explanation as to what abbreviation it is for. Change to “The gastrointestinal (GIT) system is a ….”. There are also some punctuation errors with capital letters being used mid sentence, and words like “till” being used instead of “until”. Adding a picture to the introductory section would make it visually appealing to the readers.
In the fore-gut section, there are not any pictures and make it really long and dreadful to read by first look. The explanation of the oesophagus being occluded and recanalized is a bit hard to understand and could use some further explanation / rewording / diagrams to aid. I noticed in the GIT lecture that the rotations that occur in the mid-gut was a hard concept for me to understand, you should definitely add a gif / picture to portray this nicely to the readers.

Overall, I think the tone of the page is very dry, and doesn’t include as much information as it should. You should include more detail, and especially some background information as to how and what the structures arise from, as well as explaining the overall function it will hold in the adult.

The reference list seems really small, or most the text doesn’t seem relevantly referenced in general. You should check over the reference listings before submission. For the timeline I think it’d be better if you put the fore-gut, mid-gut, and hind-gut were put together, so that we can see the overall development, rather than the individual development of the GIT system.

----

This project overall is very good with a lot relevant information. There is some use of images and hand-drawn images that are excellent. It would be good to see more images, perhaps to complement the timeline section. It is clear the group have worked well together to create a wiki page that flows well and covers all the organs of the gastrointestinal system. All the citations formatted correctly and it is good that all the references appear in one long list at the end of the page. There is still room to add tables, maybe to summarise the timeline. Other groups who presented their timelines in a table achieved an element of wiki-sophistication. There are a few spelling errors in some of the sections (specified below) which need to be corrected so as to not interrupt the flow of information when the reader is reading it. Again, there are only minimal errors or problems with this page, overall it is excellent!

The section on the midgut is well presented and thoroughly researched, well done! It is easy to follow and the way it is described makes it easy to imagine visually. However just double check for typos, for example “to that of” is spelt “tot hat of”. Simple error that is easily fixed. These hand drawn images are excellent. The colour coding and minimal use of words is very effective in supporting the written material.

The hindgut section is also well written and there is a lot of extensive information. Also double check for spelling, mesenchyme is spelt “esenchyme” in one of the sentences. This area of the project is lacking images detracting from its readability and level of interest.

----

This project page has thus far been completed with really great effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others. The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck ☺

----

I believe more of what the page hopes to achieve could be added to the introduction. These outcomes could add to the overall understanding and experience of the page. Also, remember to at least acknowledge the historical findings, recent findings and abnormalities section in the introduction (just state how this page will attempt to cover those areas- just a suggestion though!)

The development section has an excellent choice of headings and subheadings. There is correct referencing and strong evident of significant scientific research. I do believe however that this section could be summarised with more information presented in a table. There is also an excellent addition of images and hand-drawn diagrams, which adds to the overall understanding of the section. The hand-drawn images clearly display an element of teaching at the peer level and a strong overall understanding.

More recent studies could be added to the ‘recent findings’ section. Only one is currently presented at the moment. It is well explained, correctly referenced and informative though.

I can not find a ‘historical findings’ section?

I believe more abnormalities and deformities could be also added. This section is very informative and correctly referenced. I particularly enjoyed the addition of the hand-drawn diagrams- it was clearly labelled and aided in the overall understanding. Excellent work nevertheless.

----

In this review I intend to highlight the positive features of your project while pointing out some areas that need improvement, in light of the marking criteria provided.

I really like the overview on of the topic, it is clear and succinct. However you could elaborate on some of the areas if time permits. I think a developmental time line you have presented is a great way to summaries all the information. I would also like to mention that this summary is very well referenced and gives an over view of the significant event is GIT development. However I think that this information would be best presented in a tabulated form. Perhaps you could use the following layout: Column1: Week, Column 2: Foregut, Column 3: Mid-gut, Column 4: Hind-gut. It would also be a good idea to include images or diagrams. I particularly like the hand drawn diagrams, they really compliment the text and help visualise the different stages of development.

However are two issues with this project, there is little information on current research. I suggest looking up emerging technologies, drugs, treatments for congenital abnormalities in relation to GIT development. You also need to address the topic of Historic Findings, I suggest using textbooks from the library, the UNSW library database and UNSW embryology page to discover how our understanding of GIT development began and how it has changed.

A great start to the project. Make sure you organise and structure the page under the appropriate headings before you submit the project. Good luck!!

----
Introduction is good as it describes and gives an overview about what is happening in the fetal period for foregut, midgut and hindgut. However, it would be better if it mentions that the project is focusing on fetal development, abnormalities, current researches, etc.

It is clear to separate the timeline of GIT development for hindgut, midgut and foregut. It is well-researched with much information in this section. However, it would be easier to follow if a table is used and images are included.

The hand-drawn images can explain the development well, however the blue colour for labelling is a bit difficult for reading. It would be better if a darker colour is used.

It is a good idea to explain the abnormalities in definition and the causes. Some more abnormalities can be included as well as images for better understanding.

There is only one reference in recent findings. More researches could be done in this section. Also, a section about historic findings could be included as well.

There are a few spelling errors, such as “esenchyme” in the hindgut section and “tot hat of” under midgut section. Some proof-readings are needed.

The referencing is overall good, but some more researches have to be done under some sections (abnormalities and recent findings). It is easy to follow as there is a reference list at the bottom of page.

It is overall a good project as the development during fetal period is well described. However, more information about recent findings and abnormalities could be included, with the use of images to illustrate the contents.

----

The introduction to the gastrointestinal system development is ok but needs work on as to indicate what will be covered below and any other noteworthy information. However, the introduction does briefly describe the parts of the GIT system as they reader may not be aware of all the structures. Overall, sentence structures need to be improved on as they may lead to confusion. In addition to this certain areas of development have been missed out and need to be included. The strengths and weaknesses are covered below;

====Strengths====

• The timeline of GIT development in the embryonic period has been well written and is very concise in conveying what happen in each week.

• Originality is quite important as some images have been drawn up and uploaded. These have been done well and indicate that group project contributors are showing dedication.

• Most Images have an image name and an image description.

• Referencing with in-text citations and no random references in between paragraphs.

====Weaknesses====

• Abnormalities section of the GIT system is quite lacking and so more information on defects as well as image should be provided.

• Certain organ development areas are also lacking ad need to be included with those already mentioned.

• More in-text citing should be used and not only centered in some areas.

• A tabulated form of the timeline would be useful as to allow it to be clearer.

• Some footnotes are placed in the wrong areas and should be within paragraphs and not be separated.

• Headings need to be consistent such as using the same font and size.

----

Introduction is good with brief background information on the anatomy of the GIT which is an appropriate starting point for the readers. Fetal development is also described in the introduction, however I suggest including more information on embryonic period and how that leads to fetal development so that the rest of the page can focus more on the fetal stages. I also suggest including parts of each of the major subheadings in the introduction such as the common abnormalities and the recent finding. An image illustrating different organs of GIT can also help with better understanding of the anatomy. There is no referencing in the introduction to support the information provided.
Regarding the timeline section, the information needs to be tabulated in order to make it easier to compare between organs. Another alternative is to include a small timeline for each of the organs at the beginning of each section. It is very good that each stage of the timeline has been separately referenced; this shows the extensive research that has been conducted.

The recent finding section focuses on only one study in 2006 on hedge-hog signalling pathway. There are a lot of interesting and more recent studies that can be included in this section. As a starting point, you can search for recent models that help in better understanding of GIT development.
The information under each of the foregut, midgut and hindgut is very detailed and comprehensive; however the structure does not flow through the whole page with mid-gut including different subheadings and diagrams. In my opinion you should break up the foregut and hindgut sections into smaller subheadings and use diagrams like the ones used for midgut. Potential images can also be used in these sections. Additionally, the anorectal deformities under the ‘hindgut’ section can be placed under the deformities section. The “Midgut” section includes very good information and the drawings are helpful in understanding the concept however they need to be captioned.

This project does not include historic findings. I understand that this section is a bit more difficult as it is hard to find information on it. A suggestion I can make is to search for old articles in PubMed (by adjusting the year) which can include key historical events. Review articles that summarise historic findings related to GIT development may also be helpful. The abnormalities are precisely discussed and are relevant to the topic but as mentioned before, I suggest putting all the abnormalities under one subheading to make it easier for the viewers to navigate.

Overall, the main key points are addressed in this project and the content demonstrates extensive research and a good understanding of the concept. In order to facilitate learning and to make it more interesting and understandable for viewers, some of the text can be summarised in diagrams. Dot -points can also be used in some parts instead of paragraphs. The use of hand written drawings was creative and aided in understanding however I would suggest stating that the drawing is handwritten in your page. If the drawing is copied from another image, then the source of that image needs to be included as well. Also a more complete description of the image will make it easier to understand.

----
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.
----

--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 20:38, 13 August 2014 (EST)

Alright so lets choose a topic quickly before it gets taken. I would like all of you to post 3 topics that you would like to do (here) in order of importance and the topic that gets chosen the most will win. This is the only way I could think of in order to decide, so sorry. By the way Cardiovascular is taken so we cannot do that any more. My three choices are: Gastrointestinal System, Immune System and Placenta. What are yours?

i choose renal, head and neck, GIT --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 22:22, 14 August 2014 (EST)

Im thinking GIT. Everyone so far has said GIT so I reckon that might be the best option as i think it will be relatively easy to understand and follow with the whole mid gut, hind gut formation ect.
--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 12:58, 15 August 2014 (EST)

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:16, 16 August 2014 (EST) I have just reformatted your project page heading as the major heading (single =) and capitalised the words). All page sub-heading (two ==).

z3415141: I am going to be looking up research of the midgut.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 13:08, 20 August 2014 (EST)

I choose to research on abnormalities of the GIT system--[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 13:14, 20 August 2014 (EST)

z3375627: I'm going to be doing Hind gut development research --[[User:Z3375627|Z3375627]] ([[User talk:Z3375627|talk]]) 13:10, 20 August 2014 (EST)

z3414515: I will be researching foregut. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 13:12, 20 August 2014 (EST)

Alright people lets get some work done on this project. I hope everyone could at least write up few paragraphs on their chosen section by Tuesday. Thanks :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 22:18, 30 August 2014 (EST)

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 22:47, 30 August 2014 (EST) I agree, times a wasting. While you have met the required addition of references, tarts all that is currently on your project page.

--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)The reference below might help you guys.
<pubmed>12943221</pubmed>
--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)

Is it only me or is everyone finding it hard to differentiate between embryo and fetal development?--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)

Yeh I agree there are so many times where they talk about it as one in the same thing. Just have to read really carefully as we don't want to cross over. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 14:46, 2 September 2014 (EST)

Also with what you have written so far about the oesophagus, it looks good but what are you doing about referencing. Are you just keeping a list that you will put down later or are you getting the information from the resources that you found last week?? --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 14:53, 2 September 2014 (EST)

I have my references saved on my laptop so when the time comes I can relate the information to specific reference. How are you coming along with your research so far?--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 00:08, 3 September 2014 (EST)

Just been reading heaps to make sure I get the information right. I'm trying to get a really good understanding of the midgut rotation as I believe it is a critical part in the development of the ftus. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 09:31, 3 September 2014 (EST)

I am still waiting for some information from z3375627 and z3415242. Common people get moving!!! Also I meant that in the nicest way possible :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 10:52, 3 September 2014 (EST)

I have found a picture to go with the adnormality that i am doing however i will not upload it until everyone is ok with it. I will work to add on the first abnormality i have started and done and continue to research on a second one. If i come across any useful articles for you guys i will post it on this. --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 19:02, 9 September 2014 (EST)

Show the group in class your image so we can discuss on it. Also I know everyone must be busy with mid semester exams or assessments so I appreciate the effort you guys are putting in so far. BUT do remember as soon as the mid semester exams are over we need to pick up the pace or pull up our socks for this embryology project. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 09:27, 10 September 2014 (EST)

Common people lets get a move on. I have put up some information on my section though it is on the embryo period, the fetal period is in progress and in detail. The embryo period is only there as a guideline to understand how the stomach actually attains its shape. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:47, 16 September 2014 (EST)

i have come across some research articles on omphalocele (abnormality occurs in week 10-12 YAY ) just reading through them as they are pretty long and abit difficult understanding so i'm trying to put some stuff into a paragraph or two will try and upload the stuff for it by this week sometime. cheers --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 21:50, 16 September 2014 (EST)

Alright this is the week to really get a good chunk of it done now that most of our mid sems are over. Not sure if anyone else has any good youtube videos, but because we only get one I'm gonna put this one out there relating to midgut rotation: https://www.youtube.com/watch?v=AscKR_cQExY --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 08:09, 17 September 2014 (EST)

Also we need to start our list of references so I reckon we just put them down under this heading. Leave the references at the bottom of the page ie. write above the heading references.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 08:18, 17 September 2014 (EST)

i found a simple sketch drawing of omphalocele just so we have some picture on our page but i don't want to put it on the page yet incase you guys don't like i and since we cant delete it once its up so after your approval i will put it up also i am trying to find good video on organ development since im sure alot are formed by week 10 as i have read in articlese. --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 00:42, 24 September 2014 (EST)

Apologies with my lack of input on this. I’ve added a bit of the Cloacal partitioning and deformities that I’ll expand upon. I’ve also found some great pictures on some of the other GIT deformities. If I’m unable to source permission for them, I’m happy to recreate them --[[User:Z3375627|Z3375627]] ([[User talk:Z3375627|talk]]) 07:55, 24 September 2014 (EST)

Definitely put that picture up about Omphalocele. That will work well because I'm talking about midgut herniation so if I talk about it in my stuff then I can just link it so that when you click on it goes down to the bottom of the page to where you talk about it in abnormalities. Not exactly sure how we do that but I'm sure we will work it out.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 13:02, 6 October 2014 (EST)

Hey all just wanted to note that when your referencing from now look at the editing page to see what mark does so that the references are footnotes down the bottom of the page. Obviously you will need to change the reference in the brackets but you get the point. This means that when you do this all the references will come up down the bottom of the page. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 23:34, 6 October 2014 (EST)

Not sure if we are supposed to get rid of the references that we used for our group assignment but I just did because they were taking up uneccesary space on our page. Just thought i would say this here just in case we were not meant to.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 09:17, 8 October 2014 (EST)

Everyone please take off your student signature from the group page as it looks unprofessional. Thanks guys and girls :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 10:07, 8 October 2014 (EST)

'''References'''

Won Kyu Kim, Hyun Kim, Dae Ho Ahn, Myoung Hee Kim, Hyoung Woo Park Timetable for intestinal rotation in staged human embryos and fetuses. Birth Defects Res. Part A Clin. Mol. Teratol.: 2003, 67(11);941-5 PMID:14745932. I used this in describing midgut rotation.
<gallery>

</gallery>

----

*References are missing from the overview section. Although it serves as an introduction, you can still include references to support what you're saying. Also, maybe the language of this section should be edited to be a bit more formal, like the 2nd sentence in particular
*GIT = Gastrointestinal tract, not track
*The hyphens between "foregut" etc are not needed
*The timeline is a good idea! Everything was simplified. Maybe look to see if you can add some images to this section
*Week 6 of timeline: I don't think a liver can "obtain" a colour. Look to change the wording
*Maybe to simplify the timeline section better, tabulate the findings according to time (weeks), rather than dividing it by the midgut, foregut and hind gut section. It makes it hard to follow
*Need some more work on the recent findings section. Just some tips, when researching on pubmed, there's an option to look at recent articles by customising dates to say 2012-onwards
*Many potentials for adding images to the "foregut" section. If you find that copyright is too difficult to get around, then you can sketch or trace images from textbooks and upload them
*Great effort with the drawn images in the "midgut" section! Be wary of colour choice though, as the green highlighter and blue pen can be a bit difficult to see. Otherwise think of adjusting contrast on the images to make the diagram stand out more
*Maybe think of adding a video from YouTube to show some features of GIT fetal development, like the rotations. If you do that, be sure to include the 11-digit cache code as your reference point

----
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

Talk:2014 Group Project 3

2014-10-14T15:56:32Z

Z3333429: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

‘GIT system overview’ section is good but requires more information to introduce the GIT and what the page is going to have information on. Timeline could form part of this section and could also preferable be in the form of a student drawn image or even a table. The overview section also contains no in-text citations. It’s a great idea to split the GIT into the three parts: foregut, midgut and hindgut to aid in understanding. There is not much information on recent findings without any mention of current models as well so perhaps it would be best to address this before final submission.

In the foregut section there is not much mention of blood supply or innervation as was done for midgut and hindgut. Student drawn images are very impressive and referenced correctly with the student template, description, title and copyright information. The features of the midgut section could include some histological drawings or images. The ‘abnormalities’ section does not contain many in-text citations in one of the paragraphs and could include more deformities listed and described with more images, as well as information on how to treat and manage such disorders later in life. There is also no information or images addressing historical findings or current models so this needs to be looked into.

The references are correctly done and ordered, and are present at the bottom of the page. Some of the in-text citations aren’t throughout the text like they should be, for example, in the stomach, liver and gallbladder, and oesophagus sections.

Overall, good effort so far but more extensive research needs to be conducted for models and findings and more information for Abnormalities, as well as a few minor edits to make the page present more nicely.

-----

Good introduction, initial description of fore/mid/hindgut with listing of respective structures gives the reader an anatomical starting point. Fetal development is presented in appropriate depth. There is no acknowledgement of embryonic origin, research or abnormalities. These sections should feature in the introduction to present all parts of the report in the intro. The three separate timelines defeat the purpose of a timeline. These should either be merged into a single large timeline and remain at their present location or moved to introduce the foregut/midget/hindgut sections later on. Recent findings has a single study which is covered in good detail though 2-3 more studies would allow the reader to further understand current GIT Research.

In foregut section the dot-points used should match your subheadings. For example duodenum development is covered in the stomach section but is not mentioned in the subheading resulting in its development being hard to find without trawling through the text or “Ctrl-f”. Additionally you seemed to have missed out on pancreas development entirely. Foregut could also use some more images 2-3 would be suffice. Midgut development has great information, strong table, 8/8 drawings(captions required though). Inclusion of histological features gives viewer a microscopic perspective on development. Hindgut cloaca partitioning content is well worded though references are lacking.

Anorectal deformities sections should be moved under the Deformities section. The type of dot-point style used should be standardized. Too few abnormalities in the deformities section, though after the hindgut deformities are mover there should be sufficient. There are no references supporting the possible causes of Gastroschisis. The referencing it very good unlike other pages there are no random reference subheadings. In overview format wise quite attractive, information is adequately in-depth in all sections, introduction fails to address whole page, referencing is great for a draft (exceptions being “introduction” “Liver, Gallbladder and Bile Duct”), some captions aren't present, abnormalities in development section should be moved into deformities/abnormalities section.

-----
The introduction is good as it accurately describes what the GIT system is about and the anatomical positions of the features in this system. It also briefly highlights the development stages at embryonic and fetal stages, however ‘embryonic development’ should be mentioned in a little more detail to understand how far in development the fetal stage begins. I also think the introduction should include a sentence or two describing how abnormalities in such organs can lead to these diseases. Basically a bit from each major subheading should be incorporated including current research as an introduction is a summary of the whole page. As for the ‘timeline’, it would’ve been more appropriate to place the timelines under each section, e.g foregut timeline under the ‘foregut’ subheading. This is because viewers would be confused on why there is so much difference in development in one section of the page. A glossary list should be incorporated in a separate subheading to define some of these words such as hematopoiesis so that viewers can fully grasp the information.

The information under recent findings is quite interesting and relatable to the content which is GIT fetal development. However, I believe more findings could be incorporated under this subheading. The information under each organ of the three ‘guts’ are quite detailed in fetal development which is good and shouldn’t be too difficult for the viewers to understand. However, I believe the group could include information on the function of these organs as well. The structure of the information under ‘guts’ does not flow in the sense that the midgut includes features and structure whereas the other ‘guts’ do not. The innvervation and bloody supply of the hindgut should be incorporated in a paragraph instead of being listed like that. All the deformities should be places under one subheading to make it easier for viewers to navigate. The abnormalities were also concise and related to the topic. Overall, the content is relating to the topic of the project and addresses key points. It also shows good amount of research, however there seems to be too much information in some parts which could be reduced a bit. The project needs a coherent flow of the structure.

As for images, there needs to be an image under introduction which includes all features of the GIT tract. There are a lot of potential images missing under each subheading except for the ‘midgut’ section. This shows that there has been one person working on this section or one section being focused on in comparison the others. The information used to reference the images is missing in some images such as the ‘Human- fetal week 10 sagittal plane D.jpg’ (although this is uploaded from a different user so this is understandable. However images such a ‘GIT 2.jpg’ need more information including ‘student template’ as well as the reference where the image idea may have come from. Also, if this is a hand-drawn image then please state this as one member did in ‘Week 11 midgut herniation.png’. Overall, I enjoy the use of self-drawn images as it makes it easier to show what the content is saying without going through the stress of looking for an image online that doesn’t relate to the content. However more images definitely need to be added. The use of footnotes is also good and indicates what the images are showing.

There are sections where incite referencing are used, however some sections are void of them such as the ‘introduction’ and ‘Liver, Gallbladder and Bile Duct’ (the [6],[7] should be placed next to the text not above the text. The use of a ‘references’ subheading is good the same references have been combined into one number showing that the group knows how to make the references set out. The use of a table in formatting the ‘Percentage of Foetuses Herniated’ is great and shows more that the group has done research. Overall, this is a good project and if the group makes edits based on the peer-reviews received, this could enhance their project.

-----
A good introduction to the page but only outlines the developmental part of the project. Don’t forget to include other sections as well like current findings, abnormalities, etc. Also, no need for the hyphen for foregut, midgut, and hindgut. The development timeline is really good. Its very concise and well-referenced. It could be improved by tabulating the whole thing and maybe try to fuse the three sections together. Also, add an image or drawing of the development of the system. It will definitely help in terms of understanding what is happening at each stage. On recent findings, it’s not as good as the other groups but it’s definitely a start. Most groups write about 2-4 research articles for their current findings sections. As for the development section, each section is very detailed and informative. Maybe add a few images for the foregut section because images are really helpful. As for midgut, great to see images and student drawings. Good job on that. The same can be said for the hindgut section. It’s written well but maybe put the deformities in this section with the “Deformities” section. Deformities (abnormalities) section is good. It is detailed and the image used clearly shows what the disease is like. Maybe writing about 1-2 more abnormalities would make this section better.

It terms of citation and referencing, midgut section did the best job. I recommend the other sections to look for a lot more related material. I understand that this topic was divided depending on the region of the GIT, particularly the development section, but make sure to reorganise each section to make the page coherent. As for the images, most of them are well referenced. It wouldn’t hurt to add a few more. It’s great to see a lot of student drawings. Overall, a good project page very detailed in most areas but very little in referencing. In summary, focus on adding more references, making the whole page coherent, and a few more on the abnormalities.

----
The introduction provides a good basic outline of the overview of the GIT. Although, there are no in-text citations in the introduction and all sub-headings are not included into the overview. Be wary of spelling errors such as “GIT (Gastrointestinal Track) consist of the Fore-gut, Mid-gut and Hind-gut” that should read Gastrointestinal Tract consists of the foregut, midgut and hindgut. This section would be better it was expanded upon and images were added. The timeline provides good detail, though would benefit by better formatting and organisation of the information, maybe putting it all into a table, by week will tidy it up.

Adding images for the sections will definitely be beneficial. The images hand-drawn are great, although the colours used make it hard to read. If you plan to add anymore drawings, try and use dark colours that allow for easy readability. The images already uploaded are missing copyright, referencing and “student template” information for images such as “fetal week 10 sagittal plane”. I would suggest you look up the tutorial for uploading images on the pages as Mark has extensive information for the proper steps required for uploading images.

The deformities section should be re-titled abnormalities as per the assessment criteria and would ensure the group is following similar structure from the other projects. Again, adding an image per disease would be great. Try and do about 1-2 more abnormalities. Great job on putting all the references at the bottom of the page, it makes it very neat and accessible. Overall, a good project just needs a few edits.

----
A good overview of the GIT, very descriptive. This section would need some referencing as most of this info isn’t exactly common knowledge. Some of the sentences seem too short for me e.g. I would reconfigure the third sentence and combine the fourth and fifth sentences into one: ‘The GIT (gastrointestinal tract) consists of three regions: the foregut, midgut and the hindgut. The majority of the organs are located in the foregut, including…..’. You also need to make sure not to use capital letters in the middle of sentences.

The timeline is sort of well organized; it’s good that you have it separated for each region so they’re not all muddled up together, but is the info in dot points under the week, or is it just written next to the week? It needs to be kept consistent. I feel like this section is a bit too spread out as well, a large portion of the left hand side has text, while the entire right side of the screen is empty. You could possible put in a picture showing these 3 regions of the gut to fill in the space? Or maybe format the info into a table, it would make it look more formal and structured. The proper referencing technique should also be used here, not added hyperlinks.

The recent findings area is a little sparse, so you should try to find a few more. The title does say findings (plural), so maybe add at least one more. The foregut section is very extensive on the information provided which is good, a lot of research has been made. Visually however, it looks a little bad as all that can be seen is a mass of text. This can be alleviated if the same thing is done as has been with the midgut and hindgut region: the use of bullet points, a small table and the use of images to offset the slabs of text. It makes it more visually appealing. Unlike the midgut portion of the page, if the images are hand drawn, make sure they are clear, legible, and with colours used that will not strain the eye. For the images drawn in that section are messy and the labels hard to read both due to the colour of the pen used and the handwriting. In both the foregut and hindgut, referencing needs to be done. There are slabs of text in both sections where no references are made.

The deformities section is good, kept simple with no extensive explanations. Are there only 2 possible deformaties? If so, might be good to write a sentence mentioning that. If not, would be good to have at least 2 more deformities listed. The image drawn in this section is very neat, I like it a lot. The only problem with it is that it’s too small, making it hard to read some of the labels.

Overall, I think this page is very well done in terms of content. You have a lot of text, but I think it could do with some more pictures especially to offset some of the large slabs of texts in some areas. Make sure the pictures you have a clear and neat, and make sure you are referencing and doing it correctly.

----

Overall this is a good project; I enjoyed the tailored diagrams and presentation of information in a succinct manner. Information is presented in a logical and coherent manner. The presentation of information into specific components such as foregut, mid gut, hind- gut is great.

The quality of research is exceptional and well presented. Specifically, the subsection of mid gut and the use of visual aids assist immensely in the translation of complex concepts into simple ones. The use of dot-points succeeds in summarizing the information into easily digestible sections. This also improves the clarity of the page. The use of subheadings also assists with the logical analysis of the project.

However, the referencing could potentially be more extensive. A further expansion on current research model and findings will prove to be instrumental in generation of a solid understanding of the project hand. I would recommend splitting recent findings into current research models and historic findings.

It would have been beneficial to see more information on the foregut section, as this would have provided a pronounced understanding of the topic at hand. It would assist in the comprehension of the data if the timeline were tabulated. Further expansion of the abnormalities would be needed. It would be great if the abnormalities in the hindgut were moved into the abnormal section. The grammar and punctuation is sound and the readability is good. The presentation of information is lucid and shows a sound understanding of the concepts involved.

----

The introduction part of this project provided a good overview of the gastrointestinal tract and its components, also mentioning briefly the changes that occur in the fetal period. However, care must be taken to not capitalise words that are not needed e.g. Foregut, Midgut, Appendix etc. Although the information in the ‘timeline’ section is relevant, its formatting needs a bit of review as there are inconsistencies between the foregut, midgut and hindgut parts. It also seems that the in-text citations have just been arbitrarily placed in chronological order, with each line having a new reference. Also, this information may be better presented in table format to improve readability. Some simple editing may be needed to fix this.

The section on ‘Recent findings’ has some good information, however the reference needs to be properly cited and maybe a couple more articles would help give this part some substance. I thought it was effective to have the GIT split into the foregut, midgut and hindgut and then detail the fetal development under those titles. This gave the page a good structure. However, adding some images, both from online and student-drawn to the foregut and hindgut sections would help improve the aesthetics of the page. The hand-drawn images on the midgut section are effective learning tools to a student, but maybe could be drawn a little neater with darker colours as the blue labelling is difficult to read. They should also be captioned. The use of a table to show midgut herniation of fetuses was a good tool as it makes the information easier to read also.

Lastly, the section on abnormalities was well-detailed and I liked that the deformities were split into a definition and cause. An image of gastrochisis may be helpful for a reader to visualise the condition though. The in-text citations in this part were properly done and a long list of references being at the end of the page made the project look neat overall. Areas of improvement may be some simple formatting changes and evening out the information across sections, however a solid project so far.

----

Gastrointestinal

In the overview section, the words “GIT” suddenly are used without any explanation as to what abbreviation it is for. Change to “The gastrointestinal (GIT) system is a ….”. There are also some punctuation errors with capital letters being used mid sentence, and words like “till” being used instead of “until”. Adding a picture to the introductory section would make it visually appealing to the readers.
In the fore-gut section, there are not any pictures and make it really long and dreadful to read by first look. The explanation of the oesophagus being occluded and recanalized is a bit hard to understand and could use some further explanation / rewording / diagrams to aid. I noticed in the GIT lecture that the rotations that occur in the mid-gut was a hard concept for me to understand, you should definitely add a gif / picture to portray this nicely to the readers.

Overall, I think the tone of the page is very dry, and doesn’t include as much information as it should. You should include more detail, and especially some background information as to how and what the structures arise from, as well as explaining the overall function it will hold in the adult.

The reference list seems really small, or most the text doesn’t seem relevantly referenced in general. You should check over the reference listings before submission. For the timeline I think it’d be better if you put the fore-gut, mid-gut, and hind-gut were put together, so that we can see the overall development, rather than the individual development of the GIT system.

----

This project overall is very good with a lot relevant information. There is some use of images and hand-drawn images that are excellent. It would be good to see more images, perhaps to complement the timeline section. It is clear the group have worked well together to create a wiki page that flows well and covers all the organs of the gastrointestinal system. All the citations formatted correctly and it is good that all the references appear in one long list at the end of the page. There is still room to add tables, maybe to summarise the timeline. Other groups who presented their timelines in a table achieved an element of wiki-sophistication. There are a few spelling errors in some of the sections (specified below) which need to be corrected so as to not interrupt the flow of information when the reader is reading it. Again, there are only minimal errors or problems with this page, overall it is excellent!

The section on the midgut is well presented and thoroughly researched, well done! It is easy to follow and the way it is described makes it easy to imagine visually. However just double check for typos, for example “to that of” is spelt “tot hat of”. Simple error that is easily fixed. These hand drawn images are excellent. The colour coding and minimal use of words is very effective in supporting the written material.

The hindgut section is also well written and there is a lot of extensive information. Also double check for spelling, mesenchyme is spelt “esenchyme” in one of the sentences. This area of the project is lacking images detracting from its readability and level of interest.

----

This project page has thus far been completed with really great effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others. The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck ☺

----

I believe more of what the page hopes to achieve could be added to the introduction. These outcomes could add to the overall understanding and experience of the page. Also, remember to at least acknowledge the historical findings, recent findings and abnormalities section in the introduction (just state how this page will attempt to cover those areas- just a suggestion though!)

The development section has an excellent choice of headings and subheadings. There is correct referencing and strong evident of significant scientific research. I do believe however that this section could be summarised with more information presented in a table. There is also an excellent addition of images and hand-drawn diagrams, which adds to the overall understanding of the section. The hand-drawn images clearly display an element of teaching at the peer level and a strong overall understanding.

More recent studies could be added to the ‘recent findings’ section. Only one is currently presented at the moment. It is well explained, correctly referenced and informative though.

I can not find a ‘historical findings’ section?

I believe more abnormalities and deformities could be also added. This section is very informative and correctly referenced. I particularly enjoyed the addition of the hand-drawn diagrams- it was clearly labelled and aided in the overall understanding. Excellent work nevertheless.

----

In this review I intend to highlight the positive features of your project while pointing out some areas that need improvement, in light of the marking criteria provided.

I really like the overview on of the topic, it is clear and succinct. However you could elaborate on some of the areas if time permits. I think a developmental time line you have presented is a great way to summaries all the information. I would also like to mention that this summary is very well referenced and gives an over view of the significant event is GIT development. However I think that this information would be best presented in a tabulated form. Perhaps you could use the following layout: Column1: Week, Column 2: Foregut, Column 3: Mid-gut, Column 4: Hind-gut. It would also be a good idea to include images or diagrams. I particularly like the hand drawn diagrams, they really compliment the text and help visualise the different stages of development.

However are two issues with this project, there is little information on current research. I suggest looking up emerging technologies, drugs, treatments for congenital abnormalities in relation to GIT development. You also need to address the topic of Historic Findings, I suggest using textbooks from the library, the UNSW library database and UNSW embryology page to discover how our understanding of GIT development began and how it has changed.

A great start to the project. Make sure you organise and structure the page under the appropriate headings before you submit the project. Good luck!!

----
Introduction is good as it describes and gives an overview about what is happening in the fetal period for foregut, midgut and hindgut. However, it would be better if it mentions that the project is focusing on fetal development, abnormalities, current researches, etc.

It is clear to separate the timeline of GIT development for hindgut, midgut and foregut. It is well-researched with much information in this section. However, it would be easier to follow if a table is used and images are included.

The hand-drawn images can explain the development well, however the blue colour for labelling is a bit difficult for reading. It would be better if a darker colour is used.

It is a good idea to explain the abnormalities in definition and the causes. Some more abnormalities can be included as well as images for better understanding.

There is only one reference in recent findings. More researches could be done in this section. Also, a section about historic findings could be included as well.

There are a few spelling errors, such as “esenchyme” in the hindgut section and “tot hat of” under midgut section. Some proof-readings are needed.

The referencing is overall good, but some more researches have to be done under some sections (abnormalities and recent findings). It is easy to follow as there is a reference list at the bottom of page.

It is overall a good project as the development during fetal period is well described. However, more information about recent findings and abnormalities could be included, with the use of images to illustrate the contents.

----

The introduction to the gastrointestinal system development is ok but needs work on as to indicate what will be covered below and any other noteworthy information. However, the introduction does briefly describe the parts of the GIT system as they reader may not be aware of all the structures. Overall, sentence structures need to be improved on as they may lead to confusion. In addition to this certain areas of development have been missed out and need to be included. The strengths and weaknesses are covered below;

====Strengths====

• The timeline of GIT development in the embryonic period has been well written and is very concise in conveying what happen in each week.

• Originality is quite important as some images have been drawn up and uploaded. These have been done well and indicate that group project contributors are showing dedication.

• Most Images have an image name and an image description.

• Referencing with in-text citations and no random references in between paragraphs.

====Weaknesses====

• Abnormalities section of the GIT system is quite lacking and so more information on defects as well as image should be provided.

• Certain organ development areas are also lacking ad need to be included with those already mentioned.

• More in-text citing should be used and not only centered in some areas.

• A tabulated form of the timeline would be useful as to allow it to be clearer.

• Some footnotes are placed in the wrong areas and should be within paragraphs and not be separated.

• Headings need to be consistent such as using the same font and size.

----

Introduction is good with brief background information on the anatomy of the GIT which is an appropriate starting point for the readers. Fetal development is also described in the introduction, however I suggest including more information on embryonic period and how that leads to fetal development so that the rest of the page can focus more on the fetal stages. I also suggest including parts of each of the major subheadings in the introduction such as the common abnormalities and the recent finding. An image illustrating different organs of GIT can also help with better understanding of the anatomy. There is no referencing in the introduction to support the information provided.
Regarding the timeline section, the information needs to be tabulated in order to make it easier to compare between organs. Another alternative is to include a small timeline for each of the organs at the beginning of each section. It is very good that each stage of the timeline has been separately referenced; this shows the extensive research that has been conducted.

The recent finding section focuses on only one study in 2006 on hedge-hog signalling pathway. There are a lot of interesting and more recent studies that can be included in this section. As a starting point, you can search for recent models that help in better understanding of GIT development.
The information under each of the foregut, midgut and hindgut is very detailed and comprehensive; however the structure does not flow through the whole page with mid-gut including different subheadings and diagrams. In my opinion you should break up the foregut and hindgut sections into smaller subheadings and use diagrams like the ones used for midgut. Potential images can also be used in these sections. Additionally, the anorectal deformities under the ‘hindgut’ section can be placed under the deformities section. The “Midgut” section includes very good information and the drawings are helpful in understanding the concept however they need to be captioned.

This project does not include historic findings. I understand that this section is a bit more difficult as it is hard to find information on it. A suggestion I can make is to search for old articles in PubMed (by adjusting the year) which can include key historical events. Review articles that summarise historic findings related to GIT development may also be helpful. The abnormalities are precisely discussed and are relevant to the topic but as mentioned before, I suggest putting all the abnormalities under one subheading to make it easier for the viewers to navigate.

Overall, the main key points are addressed in this project and the content demonstrates extensive research and a good understanding of the concept. In order to facilitate learning and to make it more interesting and understandable for viewers, some of the text can be summarised in diagrams. Dot -points can also be used in some parts instead of paragraphs. The use of hand written drawings was creative and aided in understanding however I would suggest stating that the drawing is handwritten in your page. If the drawing is copied from another image, then the source of that image needs to be included as well. Also a more complete description of the image will make it easier to understand.

----

--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 20:38, 13 August 2014 (EST)

Alright so lets choose a topic quickly before it gets taken. I would like all of you to post 3 topics that you would like to do (here) in order of importance and the topic that gets chosen the most will win. This is the only way I could think of in order to decide, so sorry. By the way Cardiovascular is taken so we cannot do that any more. My three choices are: Gastrointestinal System, Immune System and Placenta. What are yours?

i choose renal, head and neck, GIT --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 22:22, 14 August 2014 (EST)

Im thinking GIT. Everyone so far has said GIT so I reckon that might be the best option as i think it will be relatively easy to understand and follow with the whole mid gut, hind gut formation ect.
--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 12:58, 15 August 2014 (EST)

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:16, 16 August 2014 (EST) I have just reformatted your project page heading as the major heading (single =) and capitalised the words). All page sub-heading (two ==).

z3415141: I am going to be looking up research of the midgut.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 13:08, 20 August 2014 (EST)

I choose to research on abnormalities of the GIT system--[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 13:14, 20 August 2014 (EST)

z3375627: I'm going to be doing Hind gut development research --[[User:Z3375627|Z3375627]] ([[User talk:Z3375627|talk]]) 13:10, 20 August 2014 (EST)

z3414515: I will be researching foregut. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 13:12, 20 August 2014 (EST)

Alright people lets get some work done on this project. I hope everyone could at least write up few paragraphs on their chosen section by Tuesday. Thanks :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 22:18, 30 August 2014 (EST)

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 22:47, 30 August 2014 (EST) I agree, times a wasting. While you have met the required addition of references, tarts all that is currently on your project page.

--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)The reference below might help you guys.
<pubmed>12943221</pubmed>
--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)

Is it only me or is everyone finding it hard to differentiate between embryo and fetal development?--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:23, 2 September 2014 (EST)

Yeh I agree there are so many times where they talk about it as one in the same thing. Just have to read really carefully as we don't want to cross over. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 14:46, 2 September 2014 (EST)

Also with what you have written so far about the oesophagus, it looks good but what are you doing about referencing. Are you just keeping a list that you will put down later or are you getting the information from the resources that you found last week?? --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 14:53, 2 September 2014 (EST)

I have my references saved on my laptop so when the time comes I can relate the information to specific reference. How are you coming along with your research so far?--[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 00:08, 3 September 2014 (EST)

Just been reading heaps to make sure I get the information right. I'm trying to get a really good understanding of the midgut rotation as I believe it is a critical part in the development of the ftus. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 09:31, 3 September 2014 (EST)

I am still waiting for some information from z3375627 and z3415242. Common people get moving!!! Also I meant that in the nicest way possible :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 10:52, 3 September 2014 (EST)

I have found a picture to go with the adnormality that i am doing however i will not upload it until everyone is ok with it. I will work to add on the first abnormality i have started and done and continue to research on a second one. If i come across any useful articles for you guys i will post it on this. --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 19:02, 9 September 2014 (EST)

Show the group in class your image so we can discuss on it. Also I know everyone must be busy with mid semester exams or assessments so I appreciate the effort you guys are putting in so far. BUT do remember as soon as the mid semester exams are over we need to pick up the pace or pull up our socks for this embryology project. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 09:27, 10 September 2014 (EST)

Common people lets get a move on. I have put up some information on my section though it is on the embryo period, the fetal period is in progress and in detail. The embryo period is only there as a guideline to understand how the stomach actually attains its shape. --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 12:47, 16 September 2014 (EST)

i have come across some research articles on omphalocele (abnormality occurs in week 10-12 YAY ) just reading through them as they are pretty long and abit difficult understanding so i'm trying to put some stuff into a paragraph or two will try and upload the stuff for it by this week sometime. cheers --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 21:50, 16 September 2014 (EST)

Alright this is the week to really get a good chunk of it done now that most of our mid sems are over. Not sure if anyone else has any good youtube videos, but because we only get one I'm gonna put this one out there relating to midgut rotation: https://www.youtube.com/watch?v=AscKR_cQExY --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 08:09, 17 September 2014 (EST)

Also we need to start our list of references so I reckon we just put them down under this heading. Leave the references at the bottom of the page ie. write above the heading references.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 08:18, 17 September 2014 (EST)

i found a simple sketch drawing of omphalocele just so we have some picture on our page but i don't want to put it on the page yet incase you guys don't like i and since we cant delete it once its up so after your approval i will put it up also i am trying to find good video on organ development since im sure alot are formed by week 10 as i have read in articlese. --[[User:Z3415242|Z3415242]] ([[User talk:Z3415242|talk]]) 00:42, 24 September 2014 (EST)

Apologies with my lack of input on this. I’ve added a bit of the Cloacal partitioning and deformities that I’ll expand upon. I’ve also found some great pictures on some of the other GIT deformities. If I’m unable to source permission for them, I’m happy to recreate them --[[User:Z3375627|Z3375627]] ([[User talk:Z3375627|talk]]) 07:55, 24 September 2014 (EST)

Definitely put that picture up about Omphalocele. That will work well because I'm talking about midgut herniation so if I talk about it in my stuff then I can just link it so that when you click on it goes down to the bottom of the page to where you talk about it in abnormalities. Not exactly sure how we do that but I'm sure we will work it out.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 13:02, 6 October 2014 (EST)

Hey all just wanted to note that when your referencing from now look at the editing page to see what mark does so that the references are footnotes down the bottom of the page. Obviously you will need to change the reference in the brackets but you get the point. This means that when you do this all the references will come up down the bottom of the page. --[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 23:34, 6 October 2014 (EST)

Not sure if we are supposed to get rid of the references that we used for our group assignment but I just did because they were taking up uneccesary space on our page. Just thought i would say this here just in case we were not meant to.--[[User:Z3415141|Z3415141]] ([[User talk:Z3415141|talk]]) 09:17, 8 October 2014 (EST)

Everyone please take off your student signature from the group page as it looks unprofessional. Thanks guys and girls :) --[[User:Z3414515|Z3414515]] ([[User talk:Z3414515|talk]]) 10:07, 8 October 2014 (EST)

'''References'''

Won Kyu Kim, Hyun Kim, Dae Ho Ahn, Myoung Hee Kim, Hyoung Woo Park Timetable for intestinal rotation in staged human embryos and fetuses. Birth Defects Res. Part A Clin. Mol. Teratol.: 2003, 67(11);941-5 PMID:14745932. I used this in describing midgut rotation.
<gallery>

</gallery>

----

*References are missing from the overview section. Although it serves as an introduction, you can still include references to support what you're saying. Also, maybe the language of this section should be edited to be a bit more formal, like the 2nd sentence in particular
*GIT = Gastrointestinal tract, not track
*The hyphens between "foregut" etc are not needed
*The timeline is a good idea! Everything was simplified. Maybe look to see if you can add some images to this section
*Week 6 of timeline: I don't think a liver can "obtain" a colour. Look to change the wording
*Maybe to simplify the timeline section better, tabulate the findings according to time (weeks), rather than dividing it by the midgut, foregut and hind gut section. It makes it hard to follow
*Need some more work on the recent findings section. Just some tips, when researching on pubmed, there's an option to look at recent articles by customising dates to say 2012-onwards
*Many potentials for adding images to the "foregut" section. If you find that copyright is too difficult to get around, then you can sketch or trace images from textbooks and upload them
*Great effort with the drawn images in the "midgut" section! Be wary of colour choice though, as the green highlighter and blue pen can be a bit difficult to see. Otherwise think of adjusting contrast on the images to make the diagram stand out more
*Maybe think of adding a video from YouTube to show some features of GIT fetal development, like the rotations. If you do that, be sure to include the 11-digit cache code as your reference point

----
I think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

Talk:2014 Group Project 2

2014-10-14T15:55:42Z

Z3333429: /* Peer Reviews */

{{Template:ANAT2341Project2014discussionheader}}
==Peer Reviews==

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.

-----

The introduction provides a very informative description of the functions of the kidney and bladder. Perhaps it would be good to give some more details of the embryonic development just to quickly summarise what has been happening with the fetus up until this point. Also, maybe the introduction should introduce what the page’s content is going to cover. The order of historic findings and then developmental timeline is appropriate as historic findings can be used to compile the timeline. It would also be useful to have the timeline in a table format to make the page look neater and more simplified. Also, there is no research done on ‘historic findings’ so need to address that before final submission.

‘Current research models’ section is good but brief and requires more extensive research as only two articles are cited. There should be information on current models used to study renal development as well as current research and findings. The image in this section is well presented, with appropriate titling, referencing, image descriptions and copyright information with the student image template.
Sections 1.5-1.8 should be smaller sub headings under the larger heading ‘System Development’ and perhaps should go at the top of the page, beneath the introduction seeing as in order to understand research and historic findings, it is necessary to understand renal development first.

It is very good that there is a small section on early development, however maybe it would be better to have it more briefly explained, perhaps in the form of a student drawn diagram or presented as a table. There also is a problem with the image uploaded in the early development section, so should fix that before final submission. The ‘abnormalities’ section is also done well however more conditions should be listed and described with pictures for each one. There are also only abnormalities of the kidneys listed, so maybe it would be better to have more of the other components of the renal system as well (bladder, ureter, urethra).

Also, maybe more information regarding the anatomy of the kidneys and renal system should be added, as this is an anatomy course. Some images are also missing the student image template.
Most images are uploaded correctly with the right information, maybe more would make the page look more aesthetically pleasing as well as assist learning.

Referencing is done correctly with a numbering system and in-text citations are also correct. The in-text referencing in the ‘anatomical position’ sub section of ‘fetal development’ of the ‘Kidney’ section is not referenced appropriately so just fix that minor problem.

Overall, this is great work and should just include more information in certain sections and upload more images, preferably some student drawn images as well. Well done!

-----

The introduction is well addressed as it sufficiently describes what the renal system is about and its function. Not to mention its anatomical structure as well as the difference between the embryonic and fetal stages of development. This differentiation enables viewers to understand what the content will be focused on, which is fetal development. Also, it helps focus the viewer’s attention on how the project will be divided as the group mentions abnormalities in the last paragraph. Overall the introduction has the right amount of information from each subheading and is very easy to comprehend.

There isn’t any information under ‘historic findings’. If there are any difficulties in finding some historic findings, members of the group can go to pubmed and on the side will be dates such as 1920 that could contain key historical events when renal is entered on search. The use of a development timeline was great as they outlined the major events that occur in a concise manner. Although, I believe a glossary is needed for words like ‘metanephros’ since the viewers would not know what that is. The content under current research models is interesting and correctly describes what the studies were about. Overall, the content used in the project was relating to the topic (fetal development of the kidney) and clearly showed extensive research. I really like how the group divided the different parts of the renal system as well as describing their anatomical positions. The abnormalities listed are also interesting and very easy to understand. I’m hoping to see information under the Horseshoe kidney disease.

In terms of images, there should be an image under introduction perhaps having all features of the renal system. Most images are missing the ‘student template’ aspect of the referencing and needs to be added right away. Other aspects such as description, copyright and referencing were correct. I also like the use of footnotes to describe what the images are about, however some are missing on the page such as the one under ‘anatomical position’ and ‘urethra’. The image used for the ‘development of the kidney’ should be removed from the page as it isn’t permissible. It should be replaced with an image relating to the content and have all the correct copyright and referencing information. Overall, I like the number of images used and its significance to the renal system. They accurately relate to the content of the project.

There is use of in-cite referencing which is good, however some references are just listed and should be placed under the proper ‘references’ subheading such as the ones under ‘ureter’ and ‘renal agenesis’. Some references in the ‘references’ list are used over again and can be fixed by combining it under one reference number. To make the project even more appealing, the group could format the information under ‘developmental timeline’ or even ’historic findings’ in a table. Overall, I think this project is great and by making edits based on the peer-reviews received could enhance their project.

-----

I think that this is a great start to the project. Your project appears well researched and informative, yet there are a few areas which need improvement to ensure that your project clearly demonstrates the developmental stages of renal development. I thought that over, the introduction was a good start to the project and clearly identifies the major components of the renal system and its functions. Because this is highly descriptive, I think it would benefit from a diagram or even video which could couple your description. The developmental timeline is a good idea, however I think severely lacks content. It would be a good idea to add a table or some form of diagrammatic representation of the historical findings, and the addition of pictures would greatly benefit the clarity of your work.

The current research is quite well done and seems heavily researched. There are areas which are a little bit too wordy at times, and your paragraphs are quite long- I think it would be of great benefit if you were to reduce your paragraphs into shorter bullet points so as to convey the main ideas that you are speaking about. Also, maybe a table would assist in ensuring the clarity of your work.

Overall, I think this is a great project and is off to a good start! There are a few things that need fixing- such as the developmental timeline, but I’m sure that it will come along nicely by the time submission is due.

----

Really good introduction! It clearly outlines what is in the page. Most key points were done really well except 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”. The developmental timeline would’ve been better if it was in a table, has an image showing the major steps in development, and is within the development section of the page. Regarding the development section, very detailed and informative. It clearly outlines the development of the renal system in the fetal stage. Dividing this section into the different organs is a very smart decision. It makes it a lot less confusing to the reader. Maybe try to breakdown some of the information and use dot points. There are lots of images to give the readers a visual of the developmental process. Also, the images have captions, which is great.

Great job on the current research section. The articles chosen for current research is highly relevant to the topic and to the project. This section is written concisely and very detailed. The image really helps to understand the findings of the research. The same can be said to the abnormalities section. Each disease was written concisely and is very informative. The images really help in terms of understanding the clinical manifestation/s of each disease. Try to find information on current treatments and/or management techniques for each disease.

Looking at the images included, all of them seems to be properly uploaded except for the “Kidney ascent.jpg”. It is missing its copyright information. From what I know, images from textbooks normally can’t be used because of copyright. Other than that, all the images are relevant and function as an aid to understanding what each section is about. In regards of citation and references, everything looks good. Each section was well-researched and properly cited. Great job on organising most of your references at the bottom of the page. The page looks very clean. In summary, focus on getting the historic findings section done and just minor fixes on images. Well done!

----

In this review I will attempt to highlight the strengths of your project and identify some areas for improvement, in light of the criteria provided.

I believe the developmental timeline is a great way to summarise the major events at each stage in fetal development and serves as a simple introduction to the project. However I think it would be best if you presented this information in a tabulated format, and perhaps you should include a little more detail for each developmental stage. For instance “Week 8 – Mature kidney is formed” you could also mention some structures features that allow us to recognise that it is a mature kidney (hallmarks of a mature kidney)

I think the current research section delves into a number in interesting areas, mentioning studies investigating treatment options for congenital renal abnormalities. I think another interesting area that you could address is the molecular signalling and gene expression process that drives the underlying differentiation and development of the renal system.

The abnormalities associated with renal development in the feral period have been well researched and the information provided is well structured. However this section seems incomplete. I see a number of additional links to interesting scholarly articles. I think you should discuss some more abnormalities and divide them up into abnormalities arising in the early and late stages of fetal development. I also suggest including images or diagrams to break up the text and make the descriptive text easy to visualise.

There is has been little information added on the historic findings. This is an essential component of the project. I suggest looking at text books in the library or searching the UNSW database to find information for this section.

I really like how you have selected labeled diagrams to compliment and break up the text. Each image is relevant to the topic being discussed and the small description attached really help the reader orient them selves. Overall this project is coming along nicely. Just ensure that you are making progress on all the sections. Also only include relevant references. Finally proof read and review your work before the final submission.

----

This is an excellent introduction and gives a great expectation for the information to come later in the project. The current research models section needs to be checked for spelling and grammar. The information here is good but is also very dense and hard to follow. It would be great if you could break it up a bit with bullet points or more images or tables. This style of writing is very professional and would be perfect for a report or essay, however as a wiki page it is too hard to follow. Breaking up the information into bullet point and tables would allow you to guide the reader through a journey of renal system development.

There has clearly been a lot of research and work put into this project and that is very commendable. However on a whole, there is too much information. It’s difficult to read and grasp a wholesome understanding of the renal system when it delves too deep too quickly. One suggestion is giving a more brief explanation of the timeline of nephrogenesis, urethra, ureter and bladder development and then go into more detail in a subheading called “current research findings”. The references under the abnormalities heading should be incorporated at the very end.

----
The introduction delivers a conventional scope of the renal system, allowing the audience to understand the structure and function to the parts of this system. Maybe consider uploading a picture that would illustrate the overall information in the introduction.

The developmental timeline is a great idea that outlines the significant events and in turn helps put major events into perspective, making it more effective for students to study and understand. However maybe consider presenting this information in the table format or see if you can get a vertical/horizontal line to represent the timeline. I feel that there is not enough information in the 'Historic findings' and perhaps you could do some more research.

The "Current research" section is very detailed and shows a great amount of research of recent articles that are relevant. The images included in the current research and the abnormalities section is great as it makes reference to the topic spoken about, giving the student a further understanding of the topic. The images are referenced properly except for “Kidney ascent.jpg”, it's missing a reference.

Overall this page is coming along nicely however you need to work on your development timeline formatting it in order to present a systematic presentation as a means to make it more friendly.

----
This so far is a really good. You have all obviously done your research as well as you have got a lot of references throughout your page which again is great. The introduction is well done, clear and concise which is good. Maybe think about adding an image to make it a bit more appealing. You will obviously need to add some historic findings, but I’m sure your aware of that. The developmental timeline I think could be improved if you were to tabulate it as other projects have done that and it looks really good and more professional. The referencing is well done as it looks good having all the references down the bottom of the page. There are some references over the page which have just been listed so it may be a good idea to change this so that they are all down the bottom.

You have made a good start on the current research models. Note the buy in the line ‘One recent research paper buy Al-Odat et al.’ should be by. I don’t think you should actually reference the paper in your writing either. You should reference it but do so by using a footnote rather than actually saying the names of the people. The development of the kidney image has not worked so look at the formatting of that image.

On the bigger picture of this project something that I have noticed is that the balance of writing to images is heavily towards the information writing side. So I think it would be good if you were able to tip this balance with a few more pictures as it would make the page more appealing. I think in doing so you could add some student images as this will make the page more interesting, Also spacing your information out as at times when you look at a whole chink of writing you don’t feel like reading it, so I think spacing it out more will help.

Overall though it is a well done project. A few things such as the references that have been just listed on the page that need to go down the bottom, inclusion of some more student images, and tipping the balance of your page more in favor of images would go a long way in making your project even better. But you have done a good job so far and best of luck with the rest of it.

----

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed. The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref> insert source </ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

----

The introduction provided by this project is very good and includes in-text citations. Not only does it introduce the renal system’s components but also discusses its development briefly into the embryonic and fetal stages, focusing more on fetal. Also, by having the references as one long list at the very end of the page, this gives the project a clean and tidy look, which some of the others lack. I thought this was a great idea and very orderly.

While some sections are full of information, others are scarce or empty, such as the ‘Historical findings’ section. Some information on the development of knowledge on the renal system throughout history should be included here, maybe making use of dot points detailing specific year dates. The ‘Developmental Timeline’ provides a good overview of the system’s development, although weeks 3-5 may not be necessary as these are during the embryonic period and the focus here is on fetal development. However, it does provide an overall context which is good. This information may also be effectively translated into a table format for easier readability.

The section on ‘current research models’ was nicely written, with solid analysis of 2 research articles. Using any more articles to that level of depth may be too much information, so this is a good balance. It was very good to see the text actually explaining the accompanying image, which was labelled with a caption too. The introduction to the use of animal models and why these are important was effective also.

I particularly thought the sub-sectioning of the page into the main organs of the renal system was a smart idea rather than having the entire system as a clump of information as this way, it is easier to navigate through the information. The ‘kidney’ section was of a very high standard as the information was relevant and nicely split into different processes of fetal development such as nephrogenesis and renin production. It is very helpful as a reader to have explanations of the images used, making the page more interactive and useful. However, this is a file with a ‘Permission error’ present which would need removal due to copyright infringement; this should be sorted out before the project is due.

The following three sections on the urethra, ureter and bladder were also well-written, referenced correctly with in-text citations and the images used were relevant to the text. However, captioning the image in the urethra section would be good to give the reader knowledge of exactly what it shows. The ‘abnormalities’ section was again, well -researched and full of information, however it seems a little cluttered as lengthy references are placed under the text. Integrating these into the overall reference list at the end of the page would look clearer.

Overall, this project has been well done and there is evidence of consistency throughout the section formatting, suggesting the group members have been communicating between each other, which is good to see. Some improvements I would suggest are the use of hand-drawn images to make it easier for a student to learn off the project, and using tables to summarise some information e.g. timeline.

----
The introduction is good and describes the project well. It is good to mention the function of renal system. It would be better if it states that the website will be focused on fetal development, current research and abnormalities to give a better understanding of the content.

Information under historic findings is missing, it would be a good way to start it by looking at textbooks. Images, bullet points and table can be used for an easy understanding of this section.

Using timeline to summarise the development of kidney is a good idea, however it would be clearer if a table is used, more descriptions under each stages and some images are include. Also, some references should be included in this section.

There are a lot of details under development, current research and abnormalities. It would be easier to read if they are written in point form. It is a good idea to divide renal system into several parts (kidney, urethra…) for the explanation of development. For the abnormalities, it is well-researched but some of the details are missing. It would be better if the each type of abnormalities is discussed equally.

Regarding the images, it is good and clear to explain each of them. The only problem is that there is no copyright information under the file “kidney ascent.jpg”.

The project is informative but lacking some information under historic findings and the developmental timeline.

----

The introduction of Group 2 is very succinct and straight to the point. I believe it could be improved with clear subheadings- such as ‘Bladder’ or ‘Nephrons’ (only a suggestion though!). I believe the group could add what they’re page hopes to achieve (outcomes).

The timeline/develop section of this project could be improved with a better. Add the table before or after the findings of the research paper. I believe with the table, that it could be better described and more information added to it. There is a good choice of headings though, as it has been clearly classified into distinct time points. The scientific research that accompanies this section also has a very good choice of headings/sub-headings. I do believe that this section could, however, be summarised and added to the table format above. There is excellent referencing and strong evidence of significant scientific research.
I believe more recent and varying studies in the “recent research and findings’ section could be included. I also believe this section could be improved with a better layout- with clear, concise headings identifying what these studies found and when.
The historic findings section needs to be addressed/included!

The Abnormalities section is excellent. It is informative, with a good choice of abnormalities and appropriate headings/sub-headings. It has a good choice of images and is correctly referenced.

----
The introduction to renal development in the embryonic stages has been written well as it clearly summarises this and conveys to the reader what will be covered below. Furthermore, renal development flows well as the information provided is clear and concise further displaying understanding of the topic. An image could be used that can help summarise the renal development stages in the embryonic period.

====Strengths====

• Introduction written well as it summarises the concepts well.

• Some images have a description such as ‘Glomerula number in Smoke Exposed and Control offspring’.

• Headings are short and to the point.

• Abnormalities section written well with in-text citations and the use of footnotes to good effect.

• Overall structure looks good.

====Weaknesses====

• Some images do not have a description of what the image is showing or an image name. For example, the image in the urethra development section.

• Consistency is not followed to great effect such as some images push the writing to the left side and others to the right side.

• Introduction could be updated indicating that these areas in renal development are covered in detail below as well as for more detailed information to be found in articles that have referenced.

• Some references have been placed under headings in the ureter for example. These references should be put in the end so as to maintain structure and consistency.

• Minimal grammatical errors found.

• Ensure that copyright clearance checked on images as one image has been removed and should be taken note of.

• Tabulated form of the timeline could be used or a good summary image.

• Information should be added to the historic findings heading ( 1700’s and on)

----

Introduction is very well-written with a precise background on the renal system anatomy and function. There is also a brief introduction on the development of renal system in both embryonic and fetal period as well as the abnormalities that can be associated with the development of this system. Therefore the reader can gain an expectation of what is going to be included in the wiki-page by reading the introduction first. In-cite referencing is also used to support the information provided. I suggest including an image of the anatomy of organs in the renal system to make the introduction even more perfect.

The developmental timeline is a very good way to start the development section; however your timeline is missing some of the important features such as when the ureter and urethra develop. I would also recommend tabulating the data so that it looks neater. I also recommend placing the “current research models” section after the sections describing the development of different organs so that the timeline is located right before the section explaining the development of “kidney”. Dividing the development into different organs and the subheadings used (especially under the heading of “kidney”) are very appropriate and are evidence of significant research that has been done for this project. The information provided is very comprehensive; however it is all formatted in paragraphs. I would suggest using dot points or adding your own diagrams and figures to summarise the text and make it more interesting to the readers. For example the diagram used to illustrate the anatomical position is very helpful and effectively summarises the information to readers. You should also make sure that you remove the image used for the development of kidney since it cannot be used due to copyright. In addition, most images are missing the ‘student template’ so make sure the template is added.
There isn’t any information under the heading ‘historic findings’. I understand that this section is a bit more difficult than the rest. A suggestion I can make is to search for old articles in PubMed (by adjusting the year) which can include key historical events. Review articles that summarise historic findings related to renal development may also be helpful.

The content under “current research” is very interesting and relevant. A minor spelling error exists (“buy” instead of “by”). To further improve this section, I suggest searching for recent models that aid in better understanding of kidney development. The abnormalities section is very informative. Each disease is explained thoroughly and concisely. The images are also very helpful with the understanding of clinical manifestations. To improve this section, I suggest using dot-points and using more images. Make sure you include information for “Horseshoe Kidney” as well.

Overall, the content used in this project was very relevant and showed extensive research and understanding. The use of headings and subheadings was very appropriate which showed that the work has been well-divided among members. The use of in-cite referencing is also very good and references are all listed under one subheading; however, some references are used more than once, this can be fixed and they can be all combined under one number.

----

[[RENAL SYSTEM]]

Introduction
Background
Timeline of development - everyone will research first to get general idea of when,what and how long it will develop. Divide this area up from there.
Development of Actual system - all organs and parts that contribute to it (will be divided up later)
Abnormalities

ACTUAL RESEARCH FIRST, THEN DIVIDE. SEE HOW MUCH INFO AND PARTS THERE IS FIRST

-----

This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

==ANNOUNCEMENTS==
http://www.ehd.org/science_main.php?level=a&submit3.x=73&submit3.y=21&s18=on&ops=&re=on&L1=1&L2=0 have a look at this web site, good time line --[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:50, 26 August 2014 (EST)

Looks good. There wont be much we can say for all the individual events that occur since all of it is up to the 8th week, but it'll give us a good starting point. We can say 'such and such has been formed during the embryo period' and we can move on from there. I also found the following site which gives a nice intro into the components of the renal system and some general info on each part. Thought we might be able to incorporate a bit of it, talk about what the system/organ does, then follow on how it develops. Use it as a bit of a guide to how we could do our own. http://www.myvmc.com/anatomy/urinary-system-renal-system/ --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 13:48, 24 August 2014 (EST)

https://docs.google.com/viewer?url=http%3A%2F%2Fpediatrics.med.unc.edu%2Feducation%2Fcurrent-residents%2Frotation-information%2Fnephrology%2Ffiles-1%2FNephrogenesis.ppt this web site goes into quite a lot of detail regarding how the renal system develops.

I think in terms of dividing the work:
*1- urine formation (week 11~12) & amniotic sac
*2- kidneys descending from where they developed to adult anatomical positions (week 9)
*3- development of trigone of the bladder and allantois
*4- structures that arise from the Metanephric mesoderm
*5- structures that arise from the Ureteric bud
*6- abnormalities (developmental and genetic)
*7- introduction
*8- timeline of events in development

I've thought of 8 topics we can divide the work into, so lets choose 2 each?
I preferably want to do abnormalities and urine formation (number 1 and 6), is that ok? we need this sorted out for our lab homework thing for this week. please reply asap. --[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:50, 26 August 2014 (EST)

On the actual project page when you expand the bit at the top there are 5 bullet point but the first one is just to come up with our title, shall we divide our project into those 4 different headings?:
Review that system development during the fetal period.
Identify current research models and finding.
Identify historic findings.
Identify abnormalities that can occur in this system during the fetal period

Hey guys, i have now gone and updated the page and added sub-headings as suggested by above, please feel free to add or delete anything you seem unfit for the page. As for the online assessment due tomorrow, i agree that 2 each is appropriate although the timeline will be very long and would be unfair if one person to do the whole thing... We should probably divide the timetable based on weeks and then assign who wants to do what. Although i thought we agreed that i would do the abnormalities as discussed in the last lab...? i have already started to do some research on the topic....

Here is a basic summary of some of the development structures in the renal system, as well as their abnormalities
https://web.duke.edu/anatomy/embryology/urogenital/urogenital.html

--[[User:Z3465141|Z3465141]] ([[User talk:Z3465141|talk]]) 16:52, 26 August 2014 (EST)

Ill look at 4 and 5 if that is alright with everyone (structures that arise from the Metanephric mesoderm
and the Ureteric bud), I think we need to also write a bit about Historic findings and current research models
--[[User:Z5030311|Z5030311]] ([[User talk:Z5030311|talk]]) 17:24, 26 August 2014 (EST)

I can do the descending of the kidneys and the development of the bladder (2 and 3) if everyone is fine with that --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 18:39, 26 August 2014 (EST)

Uh I guess that leaves 1 & 8 then, since no one wants to do the timeline xD
It doesnt look too hard so i dont mind doing timeline :)
so whoever only took 1 topic, can you please do the intro as well please?
Also im not 100% on the topics, but it'll have to do for now. add as we go i guess.
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 20:26, 26 August 2014 (EST)

yeah no worries, there will most likely be changes to the topics, or at least the headings. It's only set out the way it is now just so we can have a general layout, have some idea what to research. I also dont think we'll end up sticking to the subheading we chose, as there is a lot of stuff that will cross over to other topics.
I think we said that the timeline would be one of the last things we would do yeah? cause after we research all the organs and stuff as it develops, it would be easier to determine when it all develops as well, so we could just stick all that info together at the end. --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 21:04, 26 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:53, 27 August 2014 (EST)
*kidney(nephrogenesis0 - Sam
*ureter - Bahar
*urethra & fetal urination - Emily
*bladder - Rachel

*intro - Emily
*historic findings - Emily
*abnormalities - Bahar
*current models - Rachel

*developmental timeline (everyone)

HOW IS EVERYONE GOING WITH THEIR PART????
www.lab.anhb.uwa.edu.au/hsd212/.../KidneyDevelopmentPrint.ppt
--> this powerpoint gives a good general intro to renal development btw if anyone wants to see?

GIRLS
are we going to keep the whole assignment as apa referencing or as harvard? --[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 01:36, 22 September 2014 (EST)

umm i guess APA since thats the actual formal type of referencing. or you can just try and structure it the way its auto generated when you type in pubmed links haha. im gonna try and put some more content up about the kidneys in a couple days and a drawing or two. ill get some historic findings done as well.--[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 21:16, 23 September 2014 (EST)

hey guys, sorry i havent been putting anything up recently. i moved in to my new place over the weekend but the internet isnt up yet so i havent been able to upload anything. i dont know how much longer until its up, so ill be coming to uni just to use the internet (its where i am now lol). so when did the majority of our content have to be up by? was it friday or sunday? i cant remember. --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 12:48, 1 October 2014 (EST)

i found this really good article. it mainly focuses on the kidneys but there are a couple of lines here and there where it mentions some facts about the rest of the renal system. thought u guys might wanna take a look. i dont know whether full access to the article is normal or whether i only managed it because im using the uni library internet, but if u cant access it just let me know and ill send u the article (i downloaded it haha). --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 14:15, 1 October 2014 (EST)
oh i also just found this book, it has A LOT of info about the embryology of the renal system, though half the chapters seem to be focused towards abnormalities and defects of the organs http://books.google.com.au/books?id=IKexq6xCRmIC&pg=PA542&lpg=PA542&dq=rotation+of+fetal+kidney&source=bl&ots=0O-4VfybHS&sig=3VeDlTrB9HnJsdYQLP66IKNGPDU&hl=en&sa=X&ei=1ocrVPuiIoKUoQSyroEQ&ved=0CCoQ6AEwBA#v=onepage&q=rotation%20of%20fetal%20kidney&f=false --[[User:Z3465654|Z3465654]] ([[User talk:Z3465654|talk]]) 15:10, 1 October 2014 (EST)

Hey Girls hows the "break" going? :) i was wondering how many abnormalities we should have? 3/4? Also, is it just me or can we not access some of the journals that are free on Pubmed for e.g.
http://www.ncbi.nlm.nih.gov/pubmed/11458035 ?? --[[User:Z3465141|Z3465141]] ([[User talk:Z3465141|talk]]) 19:20, 1 October 2014 (EST)

Sorry this is way too late but I think 3/4 abnormalities sound good and for references I have just been doing the automated way of the references --[[User:Z5030311|Z5030311]] ([[User talk:Z5030311|talk]]) 23:07, 7 October 2014 (EST)

Also at the moment I have done 2 research models, do you think that is enough or shall I do another one? --[[User:Z5030311|Z5030311]] ([[User talk:Z5030311|talk]]) 00:01, 8 October 2014 (EST)

----

*Great introduction! Your entire page's contents was introduced well and simple. I'm just wondering if you'd have to include more references to further justify some of the aspects you've mentioned in your explanation of the renal system development
*I noticed the historic findings have been left untouched. This section is in my opinion the trickiest because of the difficulty in finding information out there. My suggestions are to go onto pubmed and use key words like "Renal system development: a historical perspective" and then work from there. You can also adjust years to look at earlier papers from the 1920s and onwards. Also use Mark's historical textbooks on this website as a starting point, it's helpful too to see how ideas in fetal development have changed over the years
*I like how the timeline overview has been simplified. Maybe think of tabulating the findings? You can get the template for doing that off any other group project that has tables by copy and pasting, then just editing in what you need
*I wouldn't add that first like under "Current research models" but if you wanted to do that, maybe think of rewording it. An example could be: "Animal models are ideal to work with when researching renal system development due to their short gestation periods, making the identification of mutations much quicker." Although what you've said about ethics is technically true, the ethics of working with animal models are still lengthy considerations and the fact that our pages are accessed to the public, maybe something like ethics don't need to be mentioned
*Include the years of when the current research findings were discovered. Otherwise, good work on this section. Just proofread over it to fix minor errors
*Great images used throughout
*Maybe think of having some sections more concise rather than wordy by including dot points

User:Z3333429

2014-10-14T15:52:52Z

Z3333429: /* Lab 2 Assessment */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==
[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.''']]
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I also think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

User:Z3333429

2014-10-14T15:50:28Z

Z3333429: /* References */

==Lab Attendance==
Lab 1: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:52, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

Lab 2: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:03, 13 August 2014 (EST)

Lab 3: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:12, 20 August 2014 (EST)

Lab 4: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:09, 27 August 2014 (EST)

Lab 5: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:32, 3 September 2014 (EST)

Lab 6: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 10 September 2014 (EST)

Lab 7: Absent

Lab 8: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:29, 8 October 2014 (EST) (forgot to add signature for this lab, 24 September 2014)

Lab 9: --[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 11:26, 8 October 2014 (EST)

==Lab 1 Assessment==

===Article 1===
'''Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization'''<ref name=”PMID25077107”><pubmed>25077107</pubmed></ref>

====Summary====
Research was carried out to investigate the possible effect of vitamin D on human reproduction. The goal was to detect whether vitamin D levels Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether there is a correlation between vitamin D levels and implantation and clinical pregnancy rates in infertile women following IVF.

====Method====
* Participants in this investigation were 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontatrio.
* Serum 25(OH)D samples were collected within a week of oocyte retrieval from the patients.
* The vitamin D levels of the participants were measured according to serum 25-hydroxy-vitamin D (25[OH]D) levels
* Patients were classified in two categories according to serum levels of 25(OH)D: sufficient (≥ 75 nmol/L) or insufficient (< 75 nmol/L). Of the 173 patients, 54.9% presented with insufficient 25(OH)D levels and 45.1% has sufficient levels.
* A comparison was made between patient demographics and IVF cycle parameters between sufficient and insufficient groups.
* Clinical pregnancy, as identified by ultrasound following 4-5 weeks after embryo transfer; was the primary outcome measurement.

====Findings====
The research found that women who presented with sufficient 25(OH)D levels had significantly higher rates of clinical pregnancy per IVF cycle (52.5%) as compared to women with insufficient levels (34.7%). A higher rate of implantation was detected in the sufficient 25(OH)D group, however the results were not statistically significant. The research calls for further investigation the findings showed that vitamin D levels might be a predictor of clinical pregnancy and vitamin D supplementation could provide a simple and economical method of improving clinical pregnancy rates, not only in women undergoing IVF, but also across the board.

====Reference====
<pubmed>25077107</pubmed>
[http://aaem.pl/fulltxt.php?ICID=1108623 Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization]

===Article 2===
'''Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization'''<ref name=”PMID24959808”><pubmed>24959808</pubmed></ref>

====Summary====
Alcohol consumption has been identified as one of the main stimulants that negatively affect the reproductive systems of both sexes. An investigation was carried out to analyse the effect of alcohol consumption of female participants on the quality of embryos obtained through IVF programmes.

====Method====
* The study covered 54 women who received treatment due to infertility.
* Of the 54 women who participated, 42.59% consumed alcohol. Records were examined of the class of embryos (A, B and C) that each woman presented in during treatment.
* The database and statistical analyses were performed using computer software STATISTICA 7.1.

====Findings====
A statistically significant correlation was found between the occurrences of class B embryo in patients who consumed more than 25 grams of ethyl alcohol daily (72.72%). Women who consumed alcohol sporadically or those who abstained entirely from alcohol presented with 44.44% and 30% rates of class B embryos respectively. It was concluded that alcohol consumption (over 25 grams of ethyl alcohol) increases the likelihood of developing pooper quality embryos. More research should be carried out to investigate this further and it was suggested that active campaigns should be established to inform women of the negative affects of alcohol consumption on embryonic development.

====Reference====
<pubmed>24959808</pubmed>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985938/ Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization]

====References====
<references/>

--[[User:Z8600021|Mark Hill]] These are good articles and well written summaries (5/5).

==Lab 2 Assessment==

[[File:RatLungGADGABA.jpeg|framed|center|800x432px|'''Microscopic Field Image of GAD and GABA in Fetal Rat Lung Tissue.'''
Location of glutamic acid decarboxylase '''(GAD)''' and γ-aminobutyric acid '''(GABA)''' in fetal lungs of rats: Detection of antigens was used to identify the location of GAD and GABA on fetal lung tissue sections.<ref><pubmed>21152393</pubmed></ref>

'''Reference'''
<references/>

--[[User:Z8600021|Mark Hill]] This image and associated information meet the assessment criteria. I have fixed a few formatting issues with the figure referencing information. See the file history for changes. (4/5)

==Lab 3 Assessment==

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Congenital Diaphragmatic Hernia===
*[http://www.ncbi.nlm.nih.gov/pubmed/12547712 Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16483386 Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16140678 Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/22214468 Congenital diaphragmatic hernia.]

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

--[[User:Z8600021|Mark Hill]] These are all good references, I would have also liked some explanation as to why they were relevant. (4/5)

==Lab 4 Assessment==

===Cord Stem Cell Therapeutics===
'''Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury'''<ref name=”PMID24940417”><pubmed>24940417</pubmed></ref>

====Summary====
The aim of this study was to find investigate if the transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells (HUCB-MSC’s) can offer an effective therapeutic treatment of Spinal Cord Injuries (SCI) and provide evidence for clinical applications. Recent studies have shown that there are possible treatments for SCI. These studies have shown that changing the local environment following after SCI (through transplantation of umbilical cord blood stem cells and other various cells and tissues) can aid in regenerating injured nerve axons and lead to functional restoration of SCI. In this study, HUCB-MSC’s were transplanted into rat models for the treatment of SCI and the therapeutic effects were evaluated through the observed behaviour and histological changes shown in the rats.

====Method====
#HUCB was retrieved from consenting donors from the Departments of Gynaecology and Obstetrics at the First and Third Affiliated Hospitals of Zhengzhou University and Zhengzhou People’s Hospital (Zhengzhou, China). The HUCB samples were screened against the hepatitis B virus.
#46 adult female Wistar rats were used from the Experimental Animal Center of Henan (Zhengzhou, China). The rats were kept in a pathogen-free room at 25°C and humidity of 45% humidity and were 250-280g in weight.
#The Allen’s method (laminectomy of the spinous process and vertebral plates of T8-T10, exposing the dorsum of the spinal cord) was used to create the SCI rat models. After the exposing of the spinal cord at T-8-T10 a weight was dropped to simulate SCI and then the rats were separated into three groups: the injury group (received no treatment following injury), the control group (treated with saline) and the transplantation group (treated with HUCB-MSC suspension).
#The HUCB cells were isolated and screen for viability then cultured.
#The cultured HUCB-MSC’s were collected and diluted then the suspension was injected at the SCI site of the rat models. The same procedure was carried out on the control group using physiological saline.
#Following transplantation, locomotor ratings were obtained from the control and transplant groups at two and four weeks. Histological changes were observed via samples collected at week one and four. These samples were then underwent statistical analysis.

====Findings====
Following treatment, the transplantation group displayed recovery of spinal nerve function and immunohistochemistry identified that there was production of novel nerve cells at wee four. These findings suggest that transplanting HUCB-MSCs help the functional recovery of the damaged of spinal cord nerves in rats with SCI.

====Reference====
<references/>

===Vascular Shunts===
'''Foramen Ovale:''' located in the interatrial septum of the heart, allows blood to travel from the right atrium to the left atrium. Becomes fossa ovalis postnatally.

'''Ductus Venosus:''' located within the liver, becomes ligamentum venosum postnatally and allows blood from the umbilical vein to bypasses the liver and enter directly into the IVC.

'''Ductus Arteriosus:''' located within the aortich arch, allows blood to pass from the pulmonary artery into the descending aorta allowing blood from the right ventricle to bypass the non-functional lungs of the fetus. Postnatally it becomes the ligamentum arteriosum.

==Lab 5 Assessment==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - damage to lower respiratory epithelium after aspiration of Meconium in amniotic fluid <ref name="PMID10612363"><pubmed>10612363</pubmed></ref>

===References===
<references/>

==Lab 7 Assessment==
===Endocrine Development===
The signalling of Gonadotropin-releasing hormone (GnRH) is responsible for regulating the actions of the gonads. The experiments in this study show that luteinising hormone expressing gonadotropes express the GnRHR and that increases in the secretion of luteinising hormone encourages gonadotropes expressed through follicle-stimulating hormone to develop. A functional role of GnHRH was suggested because removal of GnRHR cells increased the number of GnRH neurons in the hypothalamus meaning that it played a role in defining the amount of GnRH neurons present.<ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

This study was carried out on mice models where GnRHR cells were ablated to reveal the functional role in the embryonic development of the reproductive axis. The study suggests that luteinising gonadotropes acts as target cells for GnRH neurons in the forebrain and that maturation of follicle-stimulating hormone gonadotropes is dependent on the increased secretion of luteinising hormone. The method in which gonadotropes in the anterior pituitary gland mature was revealed as GnRH neurons migrate to the forebrain in the first step, secreting GnRH at this point. This is followed by the expression of GnHRH by the luteinising hormone gonadotropes. <ref name="PMID20805495"><pubmed>20805495</pubmed></ref>

===Tooth Development===
The following embryonic layers and tissues contribute to the development of the teeth:
The ectoderm of the first pharyngeal arch and neural crest, and ectomesenchymal cells.

#Odontoblasts - mesenchymal cells derived from the neural crest responsible for the secretion of predentin which calcifies to form the dentin if the teeth.
#Ameloblasts - cells derived from the differentiation of pre-ameloblasts from inner enamel epithelium. Responsible for he production if enamel.

===References===
<references/>

==Lab 8 Assessment==
===Embryonic Development of Testes===
The gonads are derived from three sources during embryonic development:
* Mesothelium
* Underlying mesenchyme
* Primordial germ cells: undifferentiated germ cells
'''Week 3:''' During week 3, the primordial germ cells migrate towards the primitive streak.

'''Week 5:''' Proliferation of the mesothelium and underlying mesenchyme occurs during week 5 of development and the gonadal ridge begins to form as a bulge on the medial region of the mesonephros. At this stage of development the gonadal cords begin to grow into the underlying mesenchyme. The gonadal structure at this stage of development is sexually indifferent.
*Testes will form in the development of an XY embryo.

'''Week 6:''' Further migration of the primordial germ cells to the junction of the hindgut and yolk sac and then onto the gonadal ridge occurs at week 6.
The differentiation of the primordial germ cells then begins at gametogenesis.
Supporting cells are differentiated into Sertoli cells via the presence of sex-determining region Y gene – a protein-coding gene of the Y chromosome.
'''Sertoli cells:'''
*Involved in the differentiation of the male gonad
*Secrete anti-Mullerian hormones – involved in the differentiation of the internal genital organs, ducts and gonads.
*Differentiate sex-hormone-secreting cells into Leydig cells - release testosterone.
[[File:Bailey327.jpg|thumb|Transverse section of pig testicle revealing seminiferous tubules (derived from testis cords) and rete testis (derived from mesonephric tubules)]]
The gonadal cords begin differentiate into seminiferous cords or testis cords and this is controlled by the Y chromosome via testis-determining factor (TDF).

'''Week 7:''' At week 7 the testes begin to develop. Mullerian duct inhibitory factor is responsible for the obliteration of the paramesonephric duct and the mesonephric duct (Wolffian duct) begins to differentiate when acted upon by testosterone produced by the Leydig cells.

In these final stages of embryonic development, the male gonads have differentiated into two main parts:
*Mesonephric duct: differentiates into the epididymis with the portion of the mesonephric duct lying outside of the gonad becoming the ductus deferens. The rete teste are formed from the mesonephric tubules growing towards the medullary sex cords.
*Testis cords: containing the Sertoli cells and germ cells. In fetal development this will further differentiate into the seminiferous tubules – the area responsible for the production of spermatozoa during puberty in males.

===References===
''Image of transverse section of pig testicle:''

Keith, A. (1902) [[Human Embryology and Morphology]]. London: Edward Arnold.
{{Historic Disclaimer}}

==Online Assessment 9==
===Renal Group===
This page was well done and the introduction gave a clear insight into what the page was going to present. The strong point of this page was the descriptions of the developments the organs of the renal system. There were plenty of images to support the information in this section of your page that complimented the text and made it easier to read. The ‘Current Research’ section was another strong point and made the page really interesting because of the relevance to the rest of the text. I think this section in particular could spark the audience’s interest in this page. There seems to be plenty of references for each section and I think this is another real strong point of your page.

The weak point in terms of information was the ‘Historic Findings’ section. The individual in my group in charge of the ‘Historic Findings’ section found information in ‘Historic Embryo’ tab and if your group is unaware of this resource it may help. The ‘Abnormalities’ section does not yet seem to be completed and I think some of the abnormalities need to text written under their titles and some more images would make this section more interesting.

In terms of the organisation of this page, the strong point is the breaking up of the development into organs. It was a wise mood because it broke the text up into easy to understand segments with a good level of detail. The references still need to be organised particularly in the ‘Abnormalities’ section but I am sure this is something that will be handled during the finishing stages of the project.
Overall, the page has its strong points and there are only some small issues that need to be rectified to make this page perfect.

===Gastrointestinal Group===
I also think that the ‘Deformities’ section should be renamed to ‘Abnormalities’ and I am not sure if that is because it is the correct term but every lecture and similar page on the Embryology wiki uses the term ‘abnormality’ to describe abnormal developments. The page also needs to be more referenced more in some areas (e.g. the possible causes of Gastroschisis section) so as to allow your audience to read more into the text you have presented and give some citations to your information. Some sections are also suffering from a lack of information (e.g. ‘Recent Findings’ – more articles and ‘Abnormalities’ – more abnormalities) and I think some more research would definitely rectify these weak points.

I really liked the use of your own drawings in some of the sections and I think this demonstrates that you understand the concepts. My only criticism is that the images are a bit difficult to interpret because the colours are really hard to see against a white background. It would be good if you included some images from scientific literature as well to give more links to scientific papers.

Overall the page needs some more work and I think some more research and referencing will definitely go a long way in making this page better. You have the basic scaffold for you page and you only really need to develop some more detail in these areas.

===Genital Group===
The definite strengths of this page are the ‘Historic Findings’, ‘Current Models and Findings’ and ‘Abnormalities’ sections. They have plenty of detail and are well referenced but could benefit further with the addition of more images (some historic images would really make the ‘Historic Findings’ section even better). The ‘Historic Findings’ section would also be easier to follow if it were broken up (perhaps by using dot points or tables). Some of the uploaded images need captions to help explain them to the audience.

The attempt to tabulate the information in the ‘Development’ section of this page is a good way of presenting the text and makes it easier to understand. It needs to be completed and supported by more images. The inclusion of the video is also a great addition to this page but it does suffer from a lack of explanation. A brief explanation of the video or some time links in your table would make it easier for the audience to understand.

Overall your page has some great detail and it is apparent that a lot of research has been carried out to give plenty of citations to your text. An introduction to your page would be a great asset as it would introduce your page to the audience and give a general overview of what this page is presenting.

===Integumentary Group===
The introduction to this page offers a brief insight into the information presented in this wiki and is a good way to start your page. In the ‘Developmental Overview, the use of dot points to break up the text is a great way of presenting the information in conjunction with the table. The table is a really good piece of work and the images make it really interesting addition to the page.

The ‘Recent Findings’ section contains a good selection of articles but I think it could benefit from a brief description of each paper to reveal the relevance of the studies. The ‘Historic Findings’ section is well written but could also be improved by including some historic images to make it more interesting.

Overall this page is really well written with plenty of detailed text. The strong point of this page is the ‘Abnormalities’ section - it has great information and really good images to support it. It could be made even better if some more abnormalities were included. This page also benefits from its neat presentation and plenty of references.

===Endocrine Group===
The breaking down of this system into organs is a real strong point of this page and there is plenty of information under each of these subheadings. The page could benefit from a ‘Current Findings’ section or perhaps by including relevant articles under each organ.

The text in this page is great but it could really benefit from the inclusion of some more images to support the information. I can see that your group did plenty of research but in text citations need to be included with your text with a ‘References’ section at the bottom of the page to stop the reference lists scattered along the page from interrupting the flow of your page.

Overall the page is definitely well resourced and has plenty of detailed text. Along with the inclusion of images and some minor improvements with the organisation of your text, this page will become a very good finished product.

===Neural Group===
The page had plenty of detail in some of the sections especially in the ‘Abnormalities’ section. This section in particular could benefit from the use of in text citation to support the text and some images to give a visual representation of the information. It is clear that it is not yet finished so it when the rest of the abnormalities are completed I think that this could be a strong point of your page.

The ‘Current Research Models and Findings’ section has a good selection of articles but some subheadings need to be explained (e.g. ‘Future Research’). If possible, it might be beneficial to include some images break up this section but the summaries of most subheadings were very good. I think this page needs a ‘Historic Findings’ heading with the relevant information. A good place to start is to look under the ‘Historic Embryo’ tab for information.

Overall this page contained some good information but still needs some work. Focus on including a ‘Historic Findings’ subheading and in text citations to support your text.

===Musculoskeletal Group===
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.

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.

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.

User:Z3333429

2014-10-14T15:47:32Z

Z3333429:

2014 Group Project 1

2014-10-08T01:59:17Z

Z3333429: /* Congenital Diaphragmatic Hernia */

{{ANAT2341Project2014header}}

=Respiratory =

===Introduction===

The respiratory system allows the body to take in oxygen and exhale carbon dioxide. The respiratory system is formed by the endoderm. The splanchnic mesoderm develops into connective tissue, cartilage and muscle of the respiratory system. The respiratory system moves the air in from the nose to the pharynx, larynx, trachea, bronchus and alveoli, which is where gas exchange occurs. During the embryonic and fetal stage the respiratory system is developing. The embryonic stage is the first 1-8 weeks and anything after that till about week 37 or birth is the fetal stage. However the respiratory system does not carry out gas exchange until birth. Whilst the embryo or fetus are in the mother, gas exchange occurs through the placenta. Once born the lungs of the new born are drained and fill up with air automatically. The lungs do not inflate completely till about 2 weeks of the new born. The surfactant in each alveoli helps keep the lungs open and prevents it from collapsing.
The respiratory tract is divided into two main parts; the conducting zone and the respiratory zone.

===Conducting Zone===

The conducting zone is made up nose to bronchioles and its function is to filter, warm, and moisten air and conduct it into the lung. The conducting zone includes the nose, pharynx, larynx, trachea, bronchi and bronchioles. Nares are the opening into the nose and is where nasal cavity is lined with cilia, mucous membrane and consists of blood filled capillaries. The oral cavity id formed by the stomodeum, which is the depression in the embryo located between the brain and the pericardium. This depression is known as the precursor of the mouth and the anterior portion of the pituitary gland. The stomodeum is ectoderm lined depression, separates the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. The membrane later breaks down and stomodeum opens into the pharynx forms the vestibule of oral cavity.
The larynx is developed from endoderm of laryngotracheal tube. The splanchnic mesoderm is important for the development of connective tissue and muscle. The bronchi is formed in week 4 and the lung buds develop and further divide each into more divisions. The left 2 and the right 3. These bronchioles will continue to divide until 17 subdivisions. After the baby is born the the bronchiole tree further divides 6 more divisions.

===Respiratory Zone===

The respiratory zone includes the terminal bronchioles, alveolar ducts and alveoli. The respiratory zone is where the oxygen and carbon dioxide exchange with the blood. The alveolar ducts and the bronchioles cause the 10% of gas exchange. The rest of the 90% is due to the alveoli.
Terminal bronchioles are the passageway for air to pass through from the bronchioles to the alveoli (air sacs) of the lungs. The alveolar ducts allows the oxygen and the carbon dioxide to move between the lungs and bloodstream. The alveoli is where the carbon dioxide and the oxygen exchange.

=Lung Development Stages=

{| class="wikitable"
!align="center" valign="center"|Stages
!align="center" valign="center"|Features
|-
|align="center" valign="center"|Embryonic (week 4-5)
|align="center" valign="center"|Lung buds would have formed and lung lobes and the bronchopulmonary segments. The stem diverticulum will have differentiated into trachea and larynx.
|-
|align="center" valign="center"|Pseudoglandular (week 6-16)
|align="center" valign="center"|The events that occur in this stage include the formation of extensive airway branching of about 14 or more generations of branching resulting in terminal bronchioles. The conducting epithelium tubes are formed and are surrounded by thick mesenchyme. At 2 months all of the segmental bronchi would have formed. The distal structures at this stage are lined with cuboidal epithelium.
|-
|align="center" valign="center"|Canalicular (week 16 to 25)
|align="center" valign="center"|The terminal bronchioles divide into two or more respiratory bronchioles and an increase in capillaries that get in contact with the cuboidal epithelium. The beginning of alveolar epithelium development is now underway and the lung morphology has drastic changes occur. the respiratory vasculature is now being developed. the differentiation of the pulmonary epithelium results in the formation of air-blood tissue barrier. This differentiation of cells transforms into specialised cell types known as ciliated, secretory,alveolar cells type 1 and 2. It is notable that the differentiation of the future conducting airways of the lung from the future gas exchange region is noticeable.
|-
|align="center" valign="center"|Saccular (week 24- 40)
|align="center" valign="center"|The terminal sacs along with the alveolar sacs and ducts have now formed. The saccules both widen and lengthen the air sac. There is a dramatic expansion in future gas exchange region in this stage. Fibroblasts also differentiate, they can now produce extra matrix, collagen and elastin. The vascular tree is also seen to grow in length and diameter. The terminal sacs will continue to develop until well into childhood.
|-
|align="center" valign="center"|Alveolar (week 36- 8 years of age)
|align="center" valign="center"| The secondary septation occurs and a significant increase in the number and size of capillaries and alveolar. postnatally from 1-3 years the alveoli will continue to form and in asa result increasing the surface area for gas exchange.
|-
|}

===References===
<references/>
[http://www.nature.com/gimo/contents/pt1/full/gimo5.html/ Anatomy and development of oral cavity and pharynx]

<pubmed>22844507</pubmed>
<pubmed>5323506</pubmed>

[http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf/ Lung Development]

==Current Research, Models and Findings==

===Current Models===

===Current Reseach and Findings===
Current research looks at the molecular processes that underpin two important developmental stages of the lung. The lung can anatomically be divided into two parts; an upper respiratory tract and a lower respiratory tract. 1. However, physiologically, the organ can be divided into two parts 2 that occur subsequently:
# The Conducting system- consisting of all the tubular structures such as the larynx, trachea, and bronchi.
# The Functional unit- An alveolus. Alveoli (''Plural''). Specialised epithelial cell, the at which gas exchange of carbon dioxide and oxygen takes.

Much research has been undertaken to understand how each of these processes occurs individually. However, a study conducted last year shows evidence that during later stages of fetal development, when the expands, these two important processes involve co-ordinated cellular interactions and take place at a precise time within development and at a specific location [2].

By week 8, the respiratory system of the fetus is well underway and the development of the lung is at the pseudoglandular stage (see above for more information for the properties of this stage). The three germ layers (ectoderm, mesoderm and endoderm) have each contributed to the development of the lung and their involvement is crucial for regulating a cascade of sequential number of events including bronchial branching (see 1. The conducting system) and alveolar differentiation (see section 2. Functional Unit).

1. '''The Conducting system''' - The respiratory network

Branching morphogenesis is the growth and branching formation to build a treelike tubular network ending with specialized air bubbles (alveoli) as sites for gas exchange[2].

• In 2013, a review study conceptualised how we now currently understand the model of branching morphogenesis. There are currently three geometrically models proposed for the way in which the primary bronchial buds branch:

## Domain branching
## Planar bifurcation
## Orthogonal bifurcation
## Trifucation --add reference from intro

• Another recent study conducted in 2013[2], suggests that there is a correlative interaction between the lung epithelium and the surrounding plural mesenchyme. The mesenchyme secretes fibroblast growth factor (FGF10) secreted by the mesenchyme, which in turn activates its membrane receptor co-worker (FGFR2). The epithelium, sequentially then generates a small amount of GTPase (KRAS). Both these contributions are involved in a cascade of signaling pathways essential for normal branching morphogenesis of the lung.

[[File:FGF10 Expression.png|centre|400px]]

2. '''The Functional Unit'''

At the end of the conducting system or at the end of the tertiary bronchial, lie the sites of gas exchange- alveolar air sacs. This process of differentiation from building on to the branched duct to specialised alveolar cells is a process named alveolar differentiation.

• There are two alveolar cell types[2]:

## Type I alveolar cells are flat and cover more than 90% of the alveolar surface, across which gases diffuse. The exchange of carbon dioxide, CO2 for 02. However, whilst the fetus is still growing inside the uterus this gas exchange does not occur. The first

## Type II alveolar cells are cuboidal and play and crucial role in the respiratory development of the fetus post-natally. They synthesize pulmonary surfactants, lipoprotein complexes that hydrate the alveolar surface and prevent alveolar collapsing by reducing surface tension.

===References===
<references/>

<pubmed>24058167</pubmed>
<pubmed>22844507</pubmed>
<pubmed>20692626</pubmed>
<pubmed>22359491</pubmed>

[[File:Lung Models Normal vs. Diseased.png|450px]]

==Historic findings==

Historical knowledge predating modern imaging techniques has most often been confirmed by contemporary studies that provided evidence for the claims of early respiratory development. At times, theories put forward for fetal respiratory development were enhanced with further detail, whereas elsewhere paradigms were shifted and challenged due to the availability of proof otherwise <ref name="PMID23431607"><pubmed>23431607</pubmed></ref>. The understanding of the development of the upper and lower respiratory system during the fetal period from week 8 onwards, as well as their respective functions, have been around since the 19th Century <ref name="PMID16601307"><pubmed>16601307</pubmed></ref>.

[[File:Bailey282.jpg|center|500px]]

'''Surfactant'''

*1929: The earliest recorded observation regarding the necessary presence of something in the lungs was proposed by Swiss physiologist Kurt von Neergaard through experiments performed observing the surface tension within the alveoli <ref name="PMID18446178"><pubmed>18446178</pubmed></ref>. Unfortunately these findings were largely disregarded until decades later when they resurfaced in importance.

*1954: Research on warfare chemicals by Pattle, Radford and Clements led to the understanding of the physical properties of surfactant <ref name="PMID15985753"><pubmed>15985753</pubmed></ref>.

*1959: The final link to provide a sound understanding of the importance of surfactant was by Mary Ellen Avery and Jere Mead. They had published a study showing that premature neonates were dying from respiratory distress syndrome (RDS) due to insufficient pulmonary surfactant <ref name="PMID14509914"><pubmed>14509914</pubmed></ref>. The lung extracts obtained from hyaline membranes of babies with RDS showed this deficiency.

*1963: Adams et al observed that fetal lung surfactant possessed particular characteristics that indicated it came to be present within the lung due to an active secretory process, which became foundational in linking the role of Type II pneumocytes with the secretion of surfactant. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

*1994: Discovery made regarding the reversed process of clearing pulmonary fluid from the lung rather than secreting it as surfactant by the baby upon birth, was conducted by Hummer et al. The experiment was performed in mice and indicated towards neonates who die as a result of failure to clear liquid from their lungs in the first 2 days of birth. <ref name="PMID24160653"><pubmed>24160653</pubmed></ref>

[[File:Lung_historical_image.PNG|400px|thumb|Historical image of lung development]]

'''Alveoli formation'''

*An Italian scientist by the name of Marcello Malpighi (1628-1694) contributed greatly to medicine, particularly the understanding of anatomy as he was a pioneer biologist to utilise newly invented microscopes to closely observe. For this reason, he is most recognised as the discoverer of the pulmonary capillaries and alveoli. <ref name="PMID23377345"><pubmed>23377345</pubmed></ref>

*Studies of the early 1900s specifically in regards to the cellular content of alveolar wall linings indicated that there was a high presence of nucleated cells in the fetus. This led to a greater understanding in the functionality of the alveoli when just at the fetal stage. <ref name="PMID19972530"><pubmed>19972530</pubmed></ref>

*J. Ernest Frazer conducted studies to research lung development along with improving the understanding of general human anatomy during his time. <ref>Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.</ref>

*The differentiation of surrounding mesenchyme into alveoli was contained within a membrane known as the pleural cavity that was separated off the peritoneal and pericardial cavities --> When was this distinction discovered..

'''References'''
<references/>

1. Developmental Biology, 6th edition
By
Scott F Gilbert.
Swarthmore College
Sunderland (MA): Sinauer Associates; 2000.
ISBN-10: 0-87893-243-7
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK9983/ | Developmental Biology]

Comparative embryology with detail on historical understandings of early respiratory development observed in various species. Accessible through PubMed.

2. Human Embryology and Morphology, 1902
By
Arthur Keith
London: Edward Arnold.
:'''Links:''' [http://php.med.unsw.edu.au/embryology/index.php?title=Book_-_Human_Embryology_and_Morphology_2 | Human Embryology and Morphology]

Historical images of past understandings on respiratory development

3. [https://m.youtube.com/watch?v=iktuxwfGpWE YouTube]
Video explaining early respiratory development

4. Lavoisier

<pubmed>5323506</pubmed>

==Abnormalities==
===Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease)===
Newborn Respiratory Distress Syndrome (NRDS), also known as Hyaline Membrane Disease (HMD) is characterised by the lack of or inability to synthesise surfactant in the premature lung of neonates.

The incidence of NRDS occurs in babies suffering form immature lung development, usually from premature birth with increased severity and incidence in correlation to decreased gestational age <ref name="PMID20468585"><pubmed>20468585</pubmed></ref>. Preterm births do not allow for full lung maturation of the preterm infant due to process in which the respiratory system forms (from upper respiratory tree to lower). Type II Pneumocytes secrete surfactant into the alveoli, reducing surface tension and thus preventing the collapse of the alveolus – they are the last respiratory cells to differentiate. Preterm infants usually lack Type II Pneumocytes in their lung tissue causing the instability of their alveoli, oedema from immature alveolar capillaries and hyaline membrane formation<ref name="PMID6071188"><pubmed>6071188</pubmed></ref>.

NRDS mostly occurs in preterm neonates but can occur in post-term and term babies for a variety of reasons including:<ref name="PMID10829971"><pubmed>10829971</pubmed></ref>
*Intrauterine Asphyxia – commonly caused by wrapping umbilical cord around the neck of the neonate, impairing development<ref name="PMID20468585"><pubmed>20468585</pubmed></ref>
*Maternal diabetes – high levels of insulin can delay surfactant synthesis<ref name="PMID20848797"><pubmed>20848797</pubmed></ref>
*Multiple pregnancy (twins, triplets etc) – associated with high rates of preterm births and resulting lung immaturity <ref name="PMID20848797"><pubmed>20848797
</pubmed></ref>
*Rapid labour, fetal distress, placenta previa, preeclampsia, placental abruption – that impair lung maturation in final stages of pregnancy <ref name="PMID20848797"><pubmed>20848797</Pubmed></ref>
*Preterm Caesarean delivery – not allowing for lung maturation<ref name="PMID14629318"><pubmed>14629318</pubmed></ref>
*Genetic abnormalities that impair surfactant synthesis (ABCA3)<ref name="PMID15044640"><pubmed>15044640</pubmed></ref>
*Meconium Aspiration Syndrome (MAS) - causes damage to the lower respiratory tract after aspiration of Meconium in amniotic fluid<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>.

===Meconium Aspiration Syndrome (MAS)===
Meconium Aspiration Syndrome (MAS) affects newborn infants in response to some form of fetal stress during the third trimester and/or parturition, often due to: acute hypoxia, intrauterine hypoxia (often caused by the wrapping of the umbilical cord around the neck of the baby) and other physiological maturational events. <ref name="PMID10612363"><pubmed>10612363</pubmed></ref><ref name="PMID16651329"><pubmed>16651329</pubmed></ref>.[[File:Meconium_aspiration_syndrome_01.jpg|thumb|X-Ray showing Meconium Aspiration Syndrome in Newborn]]
Stress on the baby before or during labor can cause relaxation of the anal sphincter leading to expulsion of Meconium by the foetus into the surrounding amniotic fluid which can then be aspirated by the fetus, damaging the upper respiratory tract and possibly the lower respiratory tract. <ref name="PMID19399004"><pubmed>19399004</pubmed></ref>.

Problems associated with Meconium aspiration include<ref name="PMID10612363"><pubmed>10612363</pubmed></ref>:
*Pulmonary gas exchange deficiency -caused by damage to the lower respiratory tract epithelium.
*Pneumitis and pneumonia - due to chemical damage and irritation from Meconium interaction with the airways.
*Blockage of the airways

===Bronchopulmonary Dysplasia===
Bronchopulmonary dysplasia (BPD) is a common complication in the treatment of Newborn Respiratory Distress Syndrome (NRDS) in infants born more than 10 weeks premature and of low weight. Efforts to treat breathing difficulties associated with NRDS can cause damage to the vulnerable lungs of the infant<ref name="PMID22785261"><pubmed>22785261</pubmed></ref>. The complications can occur from a number of reasons following treatment<ref name="PMID1971501"><pubmed>19712501</pubmed></ref>:

*Oxygen therapy causing inflammation to the lung epithelium due to the higher amounts of oxygen administered
*Used in more critical cases because of the complications associated with this form of treatment, air pressure from ventilation machines can further damage the premature lungs.
*There is some growing evidence that genetics may play a role in the predisposition of BPD <ref name="PMID25031518"><pubmed>25031518</pubmed></ref>.
*Infections from treatments involving ventilation can also occur leading to inflammation of the upper respiratory tract.

===Cystic Fibrosis===
Cystic fibrosis (CF) is caused by a mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)<ref name="PMID24685676"><pubmed>24685676</pubmed></ref>. The defect associated with this mutation results in the excretory glands of the body producing a thick sticky mucus as well as salty sweat. The disease affects several organs in the body but mainly affects the respiratory system allowing impairing the response to bacterial infection and causing inflammation in the airways<ref name="PMID16928707"><pubmed>16928707</pubmed></ref><ref name="PMID22763554"><pubmed>22763554</pubmed></ref>. This aberrant production of mucus can lead to the mucus stasis in the pulmonary epithelium, airway plugging, inflammation and chronic bacterial infection causing the decrease in lung function.

===Laryngeal Atresia===
Laryngeal Atresia (LA) is incredibly rare and occurs as a failure of the laryngo-tracheal tube to recanalise, obstructing the upper respiratory tract leading to a larynx with no lumen<ref name="PMID14325849"><pubmed>14325849</pubmed></ref>. This can cause Congenital High Airway Obstruction Syndrome (CHAOS) <ref name="PMID2342705"><pubmed>2342705</pubmed></ref>. Genetic abnormalities have been identified as having an association with AL <ref name="PMID3566610"><pubmed>3566610</pubmed></ref>.

===Congenital High Airway Obstruction Syndrome (CHAOS)===
Congenital High Airway Obstruction Syndrome (CHAOS) is extremely rare and is the result of an obstruction to the fetal airways. This obstruction can be caused by atresia of the larynx or trachea, laryngeal cysts, laryngeal webs and subglottic stenosis<ref name="PMID22167132"><pubmed>22167132</pubmed></ref>. Reviews have revealed that most cases are fatal<ref name="PMID12778398"><pubmed>12778398</pubmed></ref> but ex-utero partum treatments (EXIT) have been successful in treating this condition<ref name="PMID9802816"><pubmed>9802816</pubmed></ref>

===Congenital Laryngeal Webs===
Similarly to Laryngeal Atresia, Congenial Laryngeal Webs (CLW) are caused by failure of the laryngo-tracheal tube to recanalise, usually at the level of the vocal chords. The lumen and vocal chords of the larynx is usually developed after the epithelium is reabsorbed but in the case of CLW, this reabsorption is incomplete leaving ‘web-like’ formations in the larynx that obstruct normal development and airflow. <ref name="PMID16798587"><pubmed>16798587</pubmed></ref>

===Congenital Pulmonary Airway Malformation===
Congenital Pulmonary Airway Malformation (CPAM) occurs at varying degrees and is defined by its location in and the level of differentiation of alveoli<ref name="PMID24672262"><pubmed>24672262</pubmed></ref>. In the cases of type I and II, CPAM involves the presence of cysts affecting the terminal bronchioles and lung parenchyma. CPAM is thought to be caused by an abnormal development of the lung bud in week 4-5 of development and leads to the malformation of the pulmonary airways via the formation of lung abscesses, pulmonary infections and the sequestration of areas of the lung<ref name="PMID21355683"><pubmed>21355683</pubmed></ref>. Recent reviews have also suggest that thyroid transcription factor 1 (TTF1) may have a role in CPAM as it is involved in the differentiation of lung epithelium and overall pulmonary development. <ref name="PMID21762550"><pubmed>21762550</pubmed></ref>.

*Type I - is defined by large multilocular cysts occurring in one of the pulmonary lobes
*Type II – define by the presence of smaller more uniform cysts.
*Type III – is defined by larger lesions that affect the lung parenchyma of en entire lobe.

===Azygos Lobe===
Azygos lobe (also known as Adam's lobe) occurs due to the aberrant formation of the azygos vein as it veers from its normal course over the apex of the right lung to penetrate the upper lobe. An accessory fissure is formed in the upper lobe and the pulmonary parenchyma located in the medial portion is identified as the Azygos Lobe. There have been three observed types of azygos lobe that are relatively harmless and present little clinical significance (except during surgery due to variations in the course of the phrenic nerve): <ref name="PMID16333920"><pubmed>16333920</pubmed></ref>.
*Upper Azygos Lobe
*Lower Azygos Lobe
*the Lobe of the Azygos Vein

===References===
<references/>

<pubmed>22151899</pubmed>
<pubmed>22214468</pubmed>
<pubmed>12547712</pubmed>

===Laryngo-tracheo-oesophageal clefts===
*[http://www.ncbi.nlm.nih.gov/pubmed/22151899 Laryngo-tracheo-oesophageal clefts]

*[http://www.ncbi.nlm.nih.gov/pubmed/19712501 Bronchopulmonary Dysplasia.]
*[http://www.ncbi.nlm.nih.gov/pubmed/19252722 Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).]
*[http://www.ncbi.nlm.nih.gov/pubmed/23886794 Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.]
*[http://www.ncbi.nlm.nih.gov/pubmed/16651329 The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.]
*[http://www.ncbi.nlm.nih.gov/pubmed/11686862 Antenatal infection/inflammation and postnatal lung maturation and injury.]

User:Z3333429

2014-10-08T00:29:36Z

Z3333429:

User:Z3333429

2014-10-08T00:28:58Z

Z3333429: