Embryology - User contributions [en-gb]

User:Z3463310

2014-10-28T23:49:09Z

Z3463310: /* LAB ATTENDANCE */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:41, 22 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:49, 29 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

===Lab 10===

'''Vision'''

Vision, or the visual system is a component of the central nervous system that allows one to process visual detail through detecting and interpreting visible light waves to build a representation of the surrounding environment. Development of the eye is mainly post-natal event, however fetal eye movements (without functional brain activity) has been observed using a fetal MRI scan.
In the research article by Veronika Schöpf et. al (2014), they use data driven methodology, magnetic resonance imaging and echo-planar imaging to show that there is a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

Fetuses around week 30 to week 36 of development were scanned, and based on a probability map, the centre of the eye was estimated and refined by mathematical morphology operations. In total, 4 types of fetal eye movements were detected, including: single, prolonged eye movement, repetitive nystagmoid eye movement, fast deviation with slow reposition eye movements and fast deviation with fast reposition eye movements.

This experiment, however, could not find a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses due to the fact that conventional fMRI paradigms used in adult settings do not capture the fetal brain settings; the developing brain is in essence a network of voltage - transmitter currents, unlike an adult brain. A fetal MRI scan was initially developed to see a fetus' ocular development and for early detection of abnormalities of the brain stem. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

[https://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Vision_Development sensory - vision development]

<references/>

2014 Group Project 2

2014-10-22T06:28:29Z

Z3463310: /* Historic findings */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm <ref name="PMID20388228"><pubmed>20388228</pubmed></ref>. Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>.

==Historic findings==
{| class="wikitable"
|- align="center" bgcolor="DDCEF2"
|'''Year''' || '''Achievement'''
|}

[http://www.sciencedirect.com/science/article/pii/S0022347643802262 glomerular development in the kidney as an index of fetal maturity 1943]
[http://www.sciencedirect.com/science/article/pii/S0022347662801036 Studies of the human fetal kidney 1: I. Development of the glomerulus 1962]
[http://link.springer.com/article/10.1007/BF00301876 The ultrastructural development of distal nephron segments in the human fetal kidney 1982]

@SAM: we can maybe use these articles? I can't find the full article for the first 2, but the abstract should be able to give us enough info as to what / how much was known about fetal kidney development in 1943, 1962, 1982 respectively.

==Developmental Timeline==

{| class="wikitable"
|-bgcolor="#9ACD32" align="centre"
|'''Week''' || '''Development'''
|-bgcolor="#F0FFF0"
| 3 || Nephrogenesis begins, pronephri formation
|-bgcolor="#F0FFF0"
| 4 || Embryonic development of ureter begins from the ureteric bud
|-bgcolor="#F0FFF0"
| 5 || Examplemetanephros formation
|-bgcolor="#F0FFF0"
| 8 || Mature kidney is formed
|-bgcolor="#F0FFF0"
| 9 || Urethral sphincter complex histologically identifiable within the urogenital sinus
|-bgcolor="#F0FFF0"
| 10 || Kidneys begin to produce urine
|-bgcolor="#F0FFF0"
| 11-12 || Degeneration of the mesonephri
|-bgcolor="#F0FFF0"
| 15 || Allantois regresses and becomes known as the urachus. Vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus.
Inner layer of smooth muscle fibres and outer layer of striated muscle layers of urethral sphincter complex developed
|-bgcolor="#F0FFF0"
| 36 || Nephrogenesis is complete, however can occur as early as week 32
|-bgcolor="#F0FFF0"
| Postnatal || Maturation of neonatal glomerular filtration
|}

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Mouse Kidney Development Cartoon.jpg|300px|thumb|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref name="PMID24656820"/>, ending between week 32-36 of gestation <ref name="PMID24488483"><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time he ureteric bud <ref name="PMID24656820"/>. The process of nephron formation is shown in the second diagram to the right <ref name="PMID24011574"><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref name="PMID24781774"><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref name"PMID24623338"><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref name="PMID24656820"/>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref name="PMID24488483"/>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref name="PMID24656820"/>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref name="PMID24022365"><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref name="PMID25036148"><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref name="PMID19871238"><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013)<ref name="PMID23408557"><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.
External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==
[[File:Ureter.jpg|600px|thumb|Renal System Development]]
The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm<ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref><ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.

By week 10, the differentiation of the ureter lining occurs in response to the molecular signals from the ureteral epithelial and mesenchymal cells. This then initiates differentiation of the early simple cuboidal ureteral epithelial cells to form the multilayered urothelium. The urothelium is covered by urothelial plaquesm that express uroplakin proteins and is impermeable to urine. Concurrently, the stromal cells, smooth muscle cells and the adventitial fibroblasts (which are later maturated to form the serosa) all give rise from the differentiated mesenchymal cells <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

The smooth muscle cells go on to be futher arranged into layers with inner circular and outer longitudinal orientation and are characterized with strong expression of α-smooth muscle actin. Together, the mechanism involved give rise to the four layers of lining present in the mature ureter; urothelium, stromal cells, smooth muscle cells, and adventitial fibroblasts <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|400px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|200px|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name="PMID23169372"/>. In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported <ref name="PMID21079243"/><ref name="PMID23169372"/>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name="PMID21079243"/>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name="PMID21079243"/>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name="PMID23169372"/>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases or 1 in 20'000-40'000 live births <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

===Horseshoe Kidney===
Horseshoe kidney is a common congenital abnormality causing a fusion of the kidneys. The abnormality occurs when the poles of the lower kidney fuse, and the kidneys develop into one structure, forming an L or U shape, instead of the distinct two separate structures <ref name="PMID18059107"><pubmed>18059107</pubmed></ref> <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. Horseshoe kidney is the most common abnormality associated with fusion, occurring in 1 in 400 infants, with males being twice as likely to develop the disease <ref name="PMID24469670"><pubmed>24469670</pubmed></ref> <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

Horseshoe kidneys are commonly positioned lower than normal kidneys, being located at the lower lumber vertebrae in between L3-L5, in front of the aorta and inferior venae cavae, and posterior to the inferior mesenteric artery, which usually crosses the isthmus. There are typically two main theories outlining the cause of this disease. The first theory suggests that while the kidneys have not yet begun their decent during week 4 of gestation (the metanephric stage), and are still located in the pelvis, the two inferior poles come into contact and thus fusion occurs in the midline, resulting in the formation of a horseshoe kidney, with a fibrous isthmus. As the kidneys are still yet to form a renal capsule, the fusion of the kidneys is associated with the fusion of the nephrogenic blastemas <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===Duplicated Ureter===
[[File:Duplicated_ureter_.jpg|400px|thumb|Duplicated Ureter]]

Duplicated ureters are the most common renal abnormality, estimated to occur in 1% of the total population, and is found to be more common in females and is a condition in which more than one ureter drains one kidney.<ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref> Ureteral duplications can be complete - in which the individual has two ureters from one kidney entering the bladder, or be incomplete, where there are two separate ureters leaving the one kidney that fuse into one tube before entering the bladder. <ref> Maria M Rodriguez (2014) Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT): Fetal and Pediatric Pathology, Early Online:1–28, 2014 </ref> Incomplete duplicated ureters often have no clinical significance other than a higher risk for urinary tract infections (UTI), however, completely duplicated ureters can present with some complications such as one of the ureters joining to the vagina or urethra instead of the bladder or to its complimentary duplicated ureter. <ref><pubmed>9017803</pubmed></ref>

The development of the ureter begins at around 4 weeks into gestation when the uteral bud branches from the Wolffian duct to extend into the nephrogenic blastema. <ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref> A study carried out on 30 children with duplicated ureters by Atwell et al. (1976) showed that 66% of children with an ureteral duplication had first degree relatives with either a complete or incompletely duplicated ureter, leading to the conclusion the defect is inherited in an autosomal dominant manner.<ref><pubmed>1013379</pubmed></ref>

<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>
<pubmed>16407023</pubmed>

<references/>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-22T06:16:20Z

Z3463310: /* Duplicated Ureter */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm <ref name="PMID20388228"><pubmed>20388228</pubmed></ref>. Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>.

==Historic findings==
{| class="wikitable"
|- align="center" bgcolor="DDCEF2"
|'''Year''' || '''Achievement'''
|}

==Developmental Timeline==

{| class="wikitable"
|-bgcolor="#9ACD32" align="centre"
|'''Week''' || '''Development'''
|-bgcolor="#F0FFF0"
| 3 || Nephrogenesis begins, pronephri formation
|-bgcolor="#F0FFF0"
| 4 || Embryonic development of ureter begins from the ureteric bud
|-bgcolor="#F0FFF0"
| 5 || Examplemetanephros formation
|-bgcolor="#F0FFF0"
| 8 || Mature kidney is formed
|-bgcolor="#F0FFF0"
| 9 || Urethral sphincter complex histologically identifiable within the urogenital sinus
|-bgcolor="#F0FFF0"
| 10 || Kidneys begin to produce urine
|-bgcolor="#F0FFF0"
| 11-12 || Degeneration of the mesonephri
|-bgcolor="#F0FFF0"
| 15 || Allantois regresses and becomes known as the urachus. Vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus.
Inner layer of smooth muscle fibres and outer layer of striated muscle layers of urethral sphincter complex developed
|-bgcolor="#F0FFF0"
| 36 || Nephrogenesis is complete, however can occur as early as week 32
|-bgcolor="#F0FFF0"
| Postnatal || Maturation of neonatal glomerular filtration
|}

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Mouse Kidney Development Cartoon.jpg|300px|thumb|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref name="PMID24656820"/>, ending between week 32-36 of gestation <ref name="PMID24488483"><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time he ureteric bud <ref name="PMID24656820"/>. The process of nephron formation is shown in the second diagram to the right <ref name="PMID24011574"><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref name="PMID24781774"><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref name"PMID24623338"><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref name="PMID24656820"/>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref name="PMID24488483"/>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref name="PMID24656820"/>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref name="PMID24022365"><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref name="PMID25036148"><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref name="PMID19871238"><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013)<ref name="PMID23408557"><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.
External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==
[[File:Ureter.jpg|600px|thumb|Renal System Development]]
The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm<ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref><ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.

By week 10, the differentiation of the ureter lining occurs in response to the molecular signals from the ureteral epithelial and mesenchymal cells. This then initiates differentiation of the early simple cuboidal ureteral epithelial cells to form the multilayered urothelium. The urothelium is covered by urothelial plaquesm that express uroplakin proteins and is impermeable to urine. Concurrently, the stromal cells, smooth muscle cells and the adventitial fibroblasts (which are later maturated to form the serosa) all give rise from the differentiated mesenchymal cells <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

The smooth muscle cells go on to be futher arranged into layers with inner circular and outer longitudinal orientation and are characterized with strong expression of α-smooth muscle actin. Together, the mechanism involved give rise to the four layers of lining present in the mature ureter; urothelium, stromal cells, smooth muscle cells, and adventitial fibroblasts <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|400px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|200px|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name="PMID23169372"/>. In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported <ref name="PMID21079243"/><ref name="PMID23169372"/>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name="PMID21079243"/>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name="PMID21079243"/>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name="PMID23169372"/>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases or 1 in 20'000-40'000 live births <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

===Horseshoe Kidney===
Horseshoe kidney is a common congenital abnormality causing a fusion of the kidneys. The abnormality occurs when the poles of the lower kidney fuse, and the kidneys develop into one structure, forming an L or U shape, instead of the distinct two separate structures <ref name="PMID18059107"><pubmed>18059107</pubmed></ref> <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. Horseshoe kidney is the most common abnormality associated with fusion, occurring in 1 in 400 infants, with males being twice as likely to develop the disease <ref name="PMID24469670"><pubmed>24469670</pubmed></ref> <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

Horseshoe kidneys are commonly positioned lower than normal kidneys, being located at the lower lumber vertebrae in between L3-L5, in front of the aorta and inferior venae cavae, and posterior to the inferior mesenteric artery, which usually crosses the isthmus. There are typically two main theories outlining the cause of this disease. The first theory suggests that while the kidneys have not yet begun their decent during week 4 of gestation (the metanephric stage), and are still located in the pelvis, the two inferior poles come into contact and thus fusion occurs in the midline, resulting in the formation of a horseshoe kidney, with a fibrous isthmus. As the kidneys are still yet to form a renal capsule, the fusion of the kidneys is associated with the fusion of the nephrogenic blastemas <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===Duplicated Ureter===
[[File:Duplicated_ureter_.jpg|400px|thumb|Duplicated Ureter]]

Duplicated ureters are the most common renal abnormality, estimated to occur in 1% of the total population, and is found to be more common in females and is a condition in which more than one ureter drains one kidney.<ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref> Ureteral duplications can be complete - in which the individual has two ureters from one kidney entering the bladder, or be incomplete, where there are two separate ureters leaving the one kidney that fuse into one tube before entering the bladder. <ref> Maria M Rodriguez (2014) Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT): Fetal and Pediatric Pathology, Early Online:1–28, 2014 </ref> Incomplete duplicated ureters often have no clinical significance other than a higher risk for urinary tract infections (UTI), however, completely duplicated ureters can present with some complications such as one of the ureters joining to the vagina or urethra instead of the bladder or to its complimentary duplicated ureter. <ref><pubmed>9017803</pubmed></ref>

The development of the ureter begins at around 4 weeks into gestation when the uteral bud branches from the Wolffian duct to extend into the nephrogenic blastema. <ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref> A study carried out on 30 children with duplicated ureters by Atwell et al. (1976) showed that 66% of children with an ureteral duplication had first degree relatives with either a complete or incompletely duplicated ureter, leading to the conclusion the defect is inherited in an autosomal dominant manner.<ref><pubmed>1013379</pubmed></ref>

<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>
<pubmed>16407023</pubmed>

<references/>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-22T06:00:19Z

Z3463310: /* Duplicated Ureter */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm <ref name="PMID20388228"><pubmed>20388228</pubmed></ref>. Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>.

==Historic findings==
{| class="wikitable"
|- align="center" bgcolor="DDCEF2"
|'''Year''' || '''Achievement'''
|}

==Developmental Timeline==

{| class="wikitable"
|-bgcolor="#9ACD32" align="centre"
|'''Week''' || '''Development'''
|-bgcolor="#F0FFF0"
| 3 || Nephrogenesis begins, pronephri formation
|-bgcolor="#F0FFF0"
| 4 || Embryonic development of ureter begins from the ureteric bud
|-bgcolor="#F0FFF0"
| 5 || Examplemetanephros formation
|-bgcolor="#F0FFF0"
| 8 || Mature kidney is formed
|-bgcolor="#F0FFF0"
| 9 || Urethral sphincter complex histologically identifiable within the urogenital sinus
|-bgcolor="#F0FFF0"
| 10 || Kidneys begin to produce urine
|-bgcolor="#F0FFF0"
| 11-12 || Degeneration of the mesonephri
|-bgcolor="#F0FFF0"
| 15 || Allantois regresses and becomes known as the urachus. Vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus.
Inner layer of smooth muscle fibres and outer layer of striated muscle layers of urethral sphincter complex developed
|-bgcolor="#F0FFF0"
| 36 || Nephrogenesis is complete, however can occur as early as week 32
|-bgcolor="#F0FFF0"
| Postnatal || Maturation of neonatal glomerular filtration
|}

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Mouse Kidney Development Cartoon.jpg|300px|thumb|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref name="PMID24656820"/>, ending between week 32-36 of gestation <ref name="PMID24488483"><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time he ureteric bud <ref name="PMID24656820"/>. The process of nephron formation is shown in the second diagram to the right <ref name="PMID24011574"><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref name="PMID24781774"><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref name"PMID24623338"><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref name="PMID24656820"/>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref name="PMID24488483"/>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref name="PMID24656820"/>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref name="PMID24022365"><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref name="PMID25036148"><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref name="PMID19871238"><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013)<ref name="PMID23408557"><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.
External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==
[[File:Ureter.jpg|600px|thumb|Renal System Development]]
The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm<ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref><ref name=”PMID17928823”><pubmed>17928823</pubmed></ref>.

By week 10, the differentiation of the ureter lining occurs in response to the molecular signals from the ureteral epithelial and mesenchymal cells. This then initiates differentiation of the early simple cuboidal ureteral epithelial cells to form the multilayered urothelium. The urothelium is covered by urothelial plaquesm that express uroplakin proteins and is impermeable to urine. Concurrently, the stromal cells, smooth muscle cells and the adventitial fibroblasts (which are later maturated to form the serosa) all give rise from the differentiated mesenchymal cells <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

The smooth muscle cells go on to be futher arranged into layers with inner circular and outer longitudinal orientation and are characterized with strong expression of α-smooth muscle actin. Together, the mechanism involved give rise to the four layers of lining present in the mature ureter; urothelium, stromal cells, smooth muscle cells, and adventitial fibroblasts <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>.

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|400px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|200px|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name="PMID23169372"/>. In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported <ref name="PMID21079243"/><ref name="PMID23169372"/>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name="PMID21079243"/>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name="PMID21079243"/>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name="PMID23169372"/>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases or 1 in 20'000-40'000 live births <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

===Horseshoe Kidney===
Horseshoe kidney is a common congenital abnormality causing a fusion of the kidneys. The abnormality occurs when the poles of the lower kidney fuse, and the kidneys develop into one structure, forming an L or U shape, instead of the distinct two separate structures <ref name="PMID18059107"><pubmed>18059107</pubmed></ref> <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. Horseshoe kidney is the most common abnormality associated with fusion, occurring in 1 in 400 infants, with males being twice as likely to develop the disease <ref name="PMID24469670"><pubmed>24469670</pubmed></ref> <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

Horseshoe kidneys are commonly positioned lower than normal kidneys, being located at the lower lumber vertebrae in between L3-L5, in front of the aorta and inferior venae cavae, and posterior to the inferior mesenteric artery, which usually crosses the isthmus. There are typically two main theories outlining the cause of this disease. The first theory suggests that while the kidneys have not yet begun their decent during week 4 of gestation (the metanephric stage), and are still located in the pelvis, the two inferior poles come into contact and thus fusion occurs in the midline, resulting in the formation of a horseshoe kidney, with a fibrous isthmus. As the kidneys are still yet to form a renal capsule, the fusion of the kidneys is associated with the fusion of the nephrogenic blastemas <ref name="PMID 24178305"><pubmed>24178305</pubmed></ref>.

<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===Duplicated Ureter===
[[File:Duplicated_ureter_.jpg|400px|thumb|Duplicated Ureter]]

Duplicated ureters are the most common renal abnormality, estimated to occur in 1% of the total population, and is found to be more common in females. <ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref> Ureteral duplications can be complete - in which the individual has two ureters from one kidney entering the bladder, or be incomplete, where there are two separate ureters leaving the one kidney that fuse into one tube before entering the bladder. <ref> Maria M Rodriguez (2014) Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT): Fetal and Pediatric Pathology, Early Online:1–28, 2014 </ref> Incompletely duplicated ureters often have no clinical significance, however, completely duplicated ureters can present with some complications such as one of the ureters joining to the vagina or urethra instead of the bladder or to its complimentary duplicated ureter. <ref><pubmed>9017803</pubmed></ref>

<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>
<pubmed>16407023</pubmed>

<references/>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

User:Z3463310

2014-10-22T01:28:26Z

Z3463310: /* Lab 10 */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:41, 22 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

===Lab 10===

'''Vision'''

Vision, or the visual system is a component of the central nervous system that allows one to process visual detail through detecting and interpreting visible light waves to build a representation of the surrounding environment. Development of the eye is mainly post-natal event, however fetal eye movements (without functional brain activity) has been observed using a fetal MRI scan.
In the research article by Veronika Schöpf et. al (2014), they use data driven methodology, magnetic resonance imaging and echo-planar imaging to show that there is a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

Fetuses around week 30 to week 36 of development were scanned, and based on a probability map, the centre of the eye was estimated and refined by mathematical morphology operations. In total, 4 types of fetal eye movements were detected, including: single, prolonged eye movement, repetitive nystagmoid eye movement, fast deviation with slow reposition eye movements and fast deviation with fast reposition eye movements.

This experiment, however, could not find a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses due to the fact that conventional fMRI paradigms used in adult settings do not capture the fetal brain settings; the developing brain is in essence a network of voltage - transmitter currents, unlike an adult brain. A fetal MRI scan was initially developed to see a fetus' ocular development and for early detection of abnormalities of the brain stem. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

[https://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Vision_Development sensory - vision development]

<references/>

User:Z3463310

2014-10-22T01:27:34Z

Z3463310: /* Lab 10 */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:41, 22 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

===Lab 10===

'''Vision'''

Vision, or the visual system is a component of the central nervous system that allows one to process visual detail through detecting and interpreting visible light waves to build a representation of the surrounding environment. Development of the eye is mainly post-natal event, however fetal eye movements (without functional brain activity) has been observed using a fetal MRI scan.
In the research article by Veronika Schöpf et. al (2014), they use data driven methodology, magnetic resonance imaging and echo-planar imaging to show that there is a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

Fetuses around week 30 to week 36 of development were scanned, and based on a probability map, the centre of the eye was estimated and refined by mathematical morphology operations. In total, 4 types of fetal eye movements were detected, including: single, prolonged eye movement, repetitive nystagmoid eye movement, fast deviation with slow reposition eye movements and fast deviation with fast reposition eye movements.

This experiment, however, could not find a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses due to the fact that conventional fMRI paradigms used in adult settings do not capture the fetal brain settings; the developing brain is in essence a network of voltage - transmitter currents, unlike an adult brain. A fetal MRI scan was initially developed to see a fetus' ocular development and for early detection of abnormalities of the brain stem. <ref> Veronika Schöpf, Thomas Schlegl, Andras Jakab, Gregor Kasprian, Ramona Woitek, Daniela Prayer, and Georg Langs (2014) The relationship between eye movement and vision develops before birth: Front Hum Neurosci. 2014; 8: 775.</ref>

<references/>

User:Z3463310

2014-10-22T01:22:45Z

Z3463310: /* ASSESSMENTS */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:41, 22 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

===Lab 10===

'''Vision'''
Vision, or the visual system is a component of the central nervous system that allows one to process visual detail through detecting and interpreting visible light waves to build a representation of the surrounding environment. Development of the eye is mainly post-natal event, however fetal eye movements (without functional brain activity) has been observed using a fetal MRI scan.
In the research article by Veronika Schöpf et. al (2014), they use data driven methodology, magnetic resonance imaging and echo-planar imaging to show that there is a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses. <ref name="PMID4183095"><pubmed>4183095</pubmed></ref>
Fetuses around week 30 to week 36 of development were scanned, and based on a probability map, the centre of the eye was estimated and refined by mathematical morphology operations. In total, 4 types of fetal eye movements were detected, including: single, prolonged eye movement, repetitive nystagmoid eye movement, fast deviation with slow reposition eye movements and fast deviation with fast reposition eye movements.
This experiment, however, could not find a link between spontaneous eye movements and functional networks in the occipital brain regions associated with vision in fetuses due to the fact that conventional fMRI paradigms used in adult settings do not capture the fetal brain settings; the developing brain is in essence a network of voltage - transmitter currents, unlike an adult brain. A fetal MRI scan was initially developed to see a fetus' ocular development and for early detection of abnormalities of the brain stem. <ref name="PMID4183095"/>

<references/>

User:Z3463310

2014-10-22T00:41:06Z

Z3463310: /* LAB ATTENDANCE */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:41, 22 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

2014 Group Project 2

2014-10-20T01:08:59Z

Z3463310: /* Developmental Timeline */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==
{|
|-bgcolor="DDCEF2"|

==Developmental Timeline==
Week 3
– nephrogenesis begins, pronephri formation

Week ~4
- embryonic development of ureter begins from the ureteric bud

Week 5
– metanephros formation

Week 8
– mature kidney is formed

Week 9
- urethral sphincter complex histologically identifiable within the urogenital sinus

Week ~10
- Kidneys begin to produce urine

Week 11-12
- degeneration of the mesonephri

Week 15
- Allantois regresses and becomes known as the urachus. Vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus.
- inner layer of smooth muscle fibres and outer layer of striated muscle layers of urethral sphincter complex developed

Week 36
– nephrogenesis is complete, however can occur as early as week 32

Postnatal
– maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm. Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref>.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|300px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>
<ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name="PMID23169372"/>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-15T01:21:12Z

Z3463310: /* Developmental Timeline */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==
{|
|-bgcolor="DDCEF2"
|

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week 9 - urethral sphincter complex histologically identifiable within the urogenital sinus

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 15 - Allantois regresses and becomes known as the urachus. Vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus.
- inner layer of smooth muscle fibres and outer layer of striated muscle layers of urethral sphincter complex developed

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm. Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref>.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|300px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-15T00:13:13Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Cartoon of female urethra and bladder.jpg|thumb|Diagram of female urethra and bladder anatomy]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm. Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref>.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>
===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|300px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

File:Cartoon of female urethra and bladder.jpg

2014-10-15T00:09:06Z

Z3463310: NIDDK. (2010). National Kidney and Urologic Diseases. Retrieved October 7, 2014, from U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES: http://kidney.niddk.nih.gov/kudiseases/pubs/udictionary/pages/A_D.aspx Copyright: The majority of information at this s...

NIDDK. (2010). National Kidney and Urologic Diseases. Retrieved October 7, 2014, from U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES: http://kidney.niddk.nih.gov/kudiseases/pubs/udictionary/pages/A_D.aspx

Copyright: The majority of information at this site is in the public domain. Unless stated otherwise, documents and files on NIH web servers can be freely downloaded and reproduced. Most documents on this server are sponsored by the NIH; however, you may encounter documents that were sponsored along with private companies and other organizations. Accordingly, other parties may retain all rights to publish or reproduce these documents or to allow others to do so. Some documents available from this server may be protected under the United States and foreign copyright laws. Permission to reproduce may be required for some definitions.

2014 Group Project 2

2014-10-15T00:03:15Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

[[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth.
As you can see in the image on the left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood; in addition the glomerular in the smoke exposed offspring are not mature and are not fully vascularised. The lack of numbers and vascularisation of the glomerular lead to fewer and less developed nephrons.
By using an animal model the study showed that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The ureter is a muscular tube structure responsible for the transportation of urine produced in the kidney to the bladder. The development of the ureter typically begins during week 4 of gestation in infants. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm. Following the migration of the ureteric bud into the metanephric mesenchyme the reciprocal interaction that occur between the tip of the ureteric bud and the metanephric mesenchyme results in the ureteric bud branching morphogenesis for the formation of the renal collecting system <ref name="PMID23408557"><pubmed>23408557</pubmed></ref>. This occurs simultaneously with the elongation of the trunk of the ureteric bud, the portion remaining outside of the metanephric mesenchyme, forming the ureter <ref name=”PMID23123402”><pubmed>23123402</pubmed></ref>.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>
===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

[[File:Urinary_Bladder_Histology.jpg|300px|thumb|left|The histology of the urinary bladder showing the different cell layers]]

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

User:Z3463310

2014-10-14T23:44:44Z

Z3463310: /* LAB ATTENDANCE */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 10:44, 15 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

User:Z3463310

2014-10-14T14:15:44Z

Z3463310: /* ASSESSMENTS */

{{StudentPage2014}}

==LAB ATTENDANCE==
--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:45, 6 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:13, 13 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:41, 20 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:08, 27 August 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 3 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:42, 10 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 12:58, 17 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:06, 24 September 2014 (EST)

--[[User:Z3463310|Z3463310]] ([[User talk:Z3463310|talk]]) 11:03, 8 October 2014 (EST)

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

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 albumin synthesis]

==ASSESSMENTS==
===Lab 1===

[http://www.ncbi.nlm.nih.gov/pubmed/10696958 influence of stress and anxiety on IVF]

Anxiety levels and profiles on personality, level of stress hormones were measured in total of 44 women; 22 of which are undergoing IVF treatment for tubal infertility and the other 22 women (fertile) as a control. Serum prolactin and cortisol were used as stress markers, and STAI questionnaires were used to measure anxiety levels in each of the women. Comparison of profiling of personalities showed the infertile women had significantly higher scores in suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than the fertile women as controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle.
In this particular study, it was concluded that infertile women when compared with fertile women showed higher stress levels and had different personality profiling results in term of suspicion, guilt, and hostility, perhaps as a result of their infertility.

[http://www.ncbi.nlm.nih.gov/pubmed/25077107 correlation with IVF implantation rates and high vitamin D levels]

Research to find correlation between vitamin D levels and successful implantation / clinical pregnancy rates in infertile women undergoing IVF treatment. Measured levels of vitamin D as determined by serum 25-hydroxy-vitamin D from total 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario.
Serum 25-hydroxy-vitamin D samples were collected within 1 week of oocyte retrieval, and they were classified either sufficient or insufficient according to how much was present. (More than 75nmol/L was classified as being sufficient). It was found that 54.9% of the 173 women trialled on had insufficient Serum 25-hydryoxy-vitamin D levels, with only 34.7% successful implantation rate. The remaining 45.1% that had sufficient serum hydroxy-vitamin D had a 52.5% implantation rate. From these results, it was concluded that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation.

===LAB 2===

[[Image:Blastocyst_Hatching_in_IVF_day_6.jpeg|600px|Blastocyst hatching]]

--[[User:Z8600021|Mark Hill]] This is a commercial image not from a research article. There is also no indication you have permission to reuse this image. The file has been deleted (0/5)

===LAB 3===

'''Urine Formation + Amniotic Sac'''

[http://www.nature.com/gim/journal/v1/n2/abs/gim199948a.html limb deformations in oligohydramnio sequence]

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore]

[http://www.sciencedirect.com/science/article/pii/S0022347657800250 the urinary excretion of amino acids and sugar in early infancy]

--[[User:Z8600021|Mark Hill]] these articles may be relevant to your research sub-heading (I assume it was Urine Formation + Amniotic Sac), but you have not formatted the reference links correctly. (4/5)

===LAB 4===
1.
Stem cells are cells that have the ability to transform and generate mature cells of a particular tissue through cell differentiation. Stem cells exist in the haematopoietic system, allowing researchers to isolate them, and use them to generate specific cells through the manipulation of cell differentiation, to use them in regenerative medicine. Stem cells and cancer cells both have the ability to self-renew themselves; meaning that tumours may potentially arise from transformation of stem cells. Haematopoietic stem cells have been shown to be responsible for regeneration of blood and immune systems, and have been used extensively in therapeutic settings.

It has been found through previous researches that haemopoietic stem cells have the ability to differentiate into non haemopoietic stem cells. Some signalling pathways that regulate stem cell growth and differentiation has been found to also control cancer cell growth; making stem cells a target of transformation for some forms of cancer. The qualities of a stem cell being self-renewal systems and long living, suggests that there is a greater chance for mutations to occur and accumulate in individual stem cells compared to most mature cells found within the body.

Tannishtha. R., Morrison. S. J., Clarke. M. F., Weissman, I. L. Stem cells, cancer, and cancer stem cells. (2001) online: nature.com

2.
''Ductus Arteriosus''
connects the pulmonary artery with the descending aortic arch.
shunts the right ventricular output away from the lungs.

''Ductus Venosus''
connects the portal sinus with the inferior vena cava.
allows blood from the umbilical vein (oxygenated) to reach the liver.

Both shunts are closed post natally.
Coceani F, Olley PM. (1988) The control of cardiovascular shunts in the fetal and perinatal period. [http://www.ncbi.nlm.nih.gov/pubmed/3052747 article]

===LAB 5===

'''Omphalocele'''

An omphalocele is a rare birth defect that occurs every 1 in 4000 ~ 7000 live births world wide. [1] [2] [3] Babies with this birth defect are born with their visceral organs (mainly the liver, and intestines) inside a thin membrane sac known as the omphalocele sac external of their abdominal cavity into the base of the umbilical cord. [1] Technically, it is a herniation of the umbilicus. It is an abnormality in the development of the gastrointestinal system at around week 9~12 of fetal development. [2] It occurs when lateral unfolding of the embryo fails for some reason, leading to the formation of a omphalocele. [3] The organs are placed inside the abdominal cavity through surgery, usually within the first half year of the child being born. [4]

Children born with this defect often have other abnormalities, often chromosomal such as a trisomy at pair 13, 18 or 21. It is unknown what causes this birth defect; some studies have found maternal age, multiple pregnancies, and number of births may increase the chance of a child being born with an omphalocele, but there are also many studies against these. [3] [4] It is thought that smoking, consumption of alcohol, and not enough dietary foliate in the mother may contribute to this birth defect. [2] The survival rate for children born with just an omphalocele and do not have any other health problems is 90%. [1]

A woman carrying a fetus with omphalocele often have high levels of alpha-fetoprotein in her body. Blood testing, detailed fetal ultrasound, ultra fast fetal MRI and a fetal echocardiogram can lead to early diagnosis of a omphalocele whilst in the fetal stage, and in many cases where it is legal, the pregnancy is terminated. [2] [4]

[1] Omphalocele | Birth Anomalies | Prognosis & Treatment . 2014. Omphalocele | Birth Anomalies | Prognosis & Treatment . [ONLINE] Available at: http://www.cincinnatichildrens.org/health/o/omphalocele/.

[2] CDC - Birth Defects, Facts about Omphalocele - NCBDDD. 2014. CDC - Birth Defects, Facts about Omphalocele - NCBDDD. [ONLINE] Available at: http://www.cdc.gov/ncbddd/birthdefects/omphalocele.html.

[3] Chung DH. Pediatric surgery. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67.

[4] Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol.2012;39:375-386.

===LAB 7===

'''1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.'''

J Patell et al. (2011) show that the processes of embryogenesis, differentiation, and maturation of the thyroid gland is essential for fetal thyroid function. Such processes combined with the HPT axis (hypothalamic-putuitary-thyroid axis) and thyroid hormone metabolism results in the regulation of thyroid hormone production and secretion. Thyroxine (T4) is seen in embryo's as early in week 4 of development, and is essential for neurogenesis. T4 concentrations are highly regulated in order to provide protection to the fetus' neurological sites including the cerebral cortex. Molecular pathways in the cell membrane are thought to regulate thyroid hormone concentrations. Research suggests that mild hypothyroxinemia therefore may lead to fetal abnormalities in neurological developments. (Hypothyroxinemia is a condition where there is limited / not enough Thyroxine hormone circulating the fetal body.)

J Patel1, K Landers,H Li, R H Mortimer1, and K Richard. Thyroid hormones and fetal neurological development(2011). Journal of endocrinology.

'''2. Identify the embryonic layers and tissues that contribute to the developing teeth.'''

The ectoderm, mesoderm and neural crest ectomesenchyme contribute to the development of teeth. Ameloblasts, cells differentiated from the ectoderm develop into teeth enamel, and the Odontoblasts, mesenchymal cells differentiated from the neural crest form predentin to further calcify and form dentin. (Ben pansky). Teeth development can be divided into five stages; lamina, placode, bud, cap and bell. (Unsw embryology 2014).

Integumentary system - tooth development. UNSW embryology. 2014.
EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM. Ben Pansky. Germ Layers And Their Derivatives.

===LAB 8===
Provide a brief time course and overview of embryonic development of either the human testis or ovary. (2-3 paragraphs)

The ovaries are the female gonadal organ, responsible for the production and protection of eggs through out puberty until menopause, as well as stimulating the production of hormones. Like the male gonads the testes, the development of the ovaries are supplied from cells of the mesothelium and primordial germ cells which migrate to the ovaries from the yolk sac. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref> The paramesonephric ducts are vital in female gonad development; forming a Y-shaped uterovaginal primordium which will aid in obtaining the adult anatomical position. <ref> Moore: The Developing Human, 9th ed. Development Of Genital System. 2011 Saunders, An Imprint of Elsevier </ref>

The female gonads develop into an identifiable organ (the ovaries) at around week 10 of embryonic life where the cortex of the ovaries become visible. The testes on the other hand can be visualized at around week 7 of development. <ref> Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D. Development of The Female Genital System: Ovarian Differentiation </ref>
Histologically, the cortex containing the parenchyma, and the medulla sharing the elements of the stroma can be identified at around week 10 <ref> human embryology organogenesis. 21.3 differentiation of the gonads </ref> Gonadal cords extend into the ovarian medulla to form a rete ovarii, which normally disappear as development progresses. The ovary is first apparent as a thickening of the coelomic epithelium at about week 6 of development. At sexual differentiation and development of the gonads, the ovaries are made up of >5 cell types; the ovarian surface epithelium, endothelial cells, mesenchymal cells, pre-granulosa cells and primordial germ cells. <ref> Peter Smith, Dagmar Wilhelm, Raymond J Rodgers. "Development of the mammalian ovary" Journal of endocrinology. June 1, 2014, pg221 </ref>

Include an image from the historic genital embryology section of the online notes in your description.

[[image:Historic-ovary.jpg]]

<references/>

===LAB 9===

Peer review

'''Respiratory'''

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.
The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

'''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.

'''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!!

'''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!

'''Endocrine'''

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!

'''Neural - CNS'''

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!

'''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!

Talk:2014 Group Project 1

2014-10-14T14:13:16Z

Z3463310: /* Peer Reviews */

{{ANAT2341Project2014discussionheader}}
==Peer Reviews==

The introduction section is very clear and informative and nicely organised. The images look great, however I think that perhaps some information should be placed alongside them to describe what each figure/image is demonstrating. Maybe a few sentences to describe an overall objective of the page can also be added for extra clarity. Lung development stages section has a great layout and is nice and easy to read. A few images added to the table may improve this section as the visualisation of this developmental process would greatly aid in the readers understanding of the topic. Referencing also needs a little work to be presented correctly. I particularly like the current research section of the page- the presentation of new findings according to different sub-topics in respiratory development is a great idea! The image itself would look better with a different placement as it seems rather isolated and again some information as to what the diagram is demonstrating would be beneficial. The historic findings section was particularly well done also, great images used and referencing is done very well. The abnormalities section was a great read, nicely organised via the subheadings and well written. Some subheadings may need a little more detail with information and maybe a few more images would also go a long way, referencing was done very well. Overall really nice page! ☺

-----

The introduction is very informative and I particularly like how it describes the embryonic development of the respiratory system as well, since in order to understand what is happening in the fetal period, it is important to first understand what happened before that in the embryonic period. Perhaps the introduction could also introduce what information the page is going to contain.

The timeline is well presented in a table form, however maybe it would be better suited to be in the introduction section. The table could also incorporate the use of histological images to illustrate the differences between the time periods. Also, the sub sections titled ‘current models’ and ‘current research and findings’ could be part of a larger section and not fall under the ‘Lung Development Stages’ section.

There is no information as yet under ‘Current models’ however extensive research seems to be conducted on ‘current research findings’. Perhaps it would be better to include more journal articles in this section. The use of dot points and numbering systems is also very effective in allowing the information to be easily read and flow. More articles also need to be covered in the ‘Historic findings section’ as it is very brief at the moment with only a few sentences on each article.

The ‘abnormalities’ section is very well done with an abundance of conditions however more images should be uploaded for each abnormality in order to see what it visually presents as in the fetus and also to make the page look nicer.

The images uploaded onto the page contain adequate information explaining them, copyright information as well as the student image template, which is good. There is one student drawn image, which is also great, but maybe some more would further illustrate the group’s understanding of their topic.

The referencing is done correctly mostly throughout the page but is scattered throughout every section so perhaps it would be better to have them in one section at the bottom of the page under the heading entitled ‘References’ and numbered as they appear in the text. In-text citations are throughout and appear to be done correctly.

Overall, this is a very good effort and a bit of editing will make the page look much more neater and organized. Keep up the great work!

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This project is extremely well done. I found the overall layout of your work to be easy to read and succinct. It captured my attention throughout the entirety of the project and was engaging with the use of bullet points. I thought your use of diagrams was great in aiding the understanding of this topic, however I thought that more diagrams or pictures could be added in order to help the reader visualize exactly what’s going on. I thought that te developmental timeline was a great idea, however could benefit from some more images or diagrams to assist in understanding the developmental stages. I thought the historic findings sections was especially well done as it appears well researched and thoroughly informative. The abnormalities was also well done, however again could benefit from the addition of a few more diagrams.

I think that with the addition of more drawings needs to be some attention to detail when referencing and stating copyright. I’ve noticed that some pictures lack copyright and some don’t have a description, making it difficult to understand the context of the picture and to envisage how it relates to the content. Whilst this is mostly self explanatory- I think that because this is an informative piece it pays to spoon-feed us a bit. Also, your referencing could use a bit of a tidy, but that can easily be fixed before submission. I think that overall this has great potential to be a wonderful project and I look forward to seeing it at its completion!

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The introduction was written quite well as it explains what the respiratory system is about and the origin of its development. It also briefly highlights the difference between the embryonic and fetal stage which is important in enabling the viewers to have an understanding on what the project will be focusing on. I also like how the group distinguished between the two zones of the respiratory tract and adequately described the features and function of each. The content in the lung development stages clearly relates to the topic and underlines fetal development. The group briefly mentioned the key features in each stage instead of pasting a whole lot of information; this makes it easier for viewers to understand. Overall the content relates to the learning objectives of embryology and the level of research is good as exemplified under ‘Current Research and Findings’ and ‘abnormalities’ (many forms of diseases described). The project however could benefit from having a ‘Glossary’ list so that viewers can understand some uncommon words.

The images under introduction and the image used for Meconium aspiration syndrome have not been referenced properly as there is missing information such as ((Template: Student Image)), description, copyright information and proper references for some. The image used under the ‘current research and findings’ subheading is a good example for the group to copy the referencing style. It is also vital that the group adds a brief description of what the image illustrates as a footnote to help viewers understand the relation of the content and image (this is seen in the image under ‘surfactant’). More images could be added such as in the ‘lung development stage’ and under abnormalities. If images for lung development stages aren’t easily accessible, it is perhaps a good idea to draw them. The table format used for ‘lung development stages’ makes it easy for the viewers to navigate which is a good feature used in the project.

In terms of referencing, there are many in-cite references missing such as in the ‘introduction’ and in ‘lung development stages’. It is important to have these references formatted correctly under the one ‘references’ subheading. There seems to be many ‘references’ subheadings making it harder for viewers to navigate. Some references are shown as ‘</span> </li> which needs to be fixed right away. Overall, the content seems well written, formatted and concise making it easy to understand. However the problems related to referencing needs to be corrected as this is inconsistent throughout the project.

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This project was done really well. All key points, i.e. development, historic findings, etc., were clearly described. In terms of content, this group did a great job. It is very informative and all information they have included are relevant to the topic. There are a few mentions of embryonic stage but I do understand why, particularly for the development of the respiratory system. The developmental timeline is good but an image about the development would make it better. Remember to add in-text citations for this part. Historic findings section is very detailed and exceptional. Abnormalities is done well. A couple or more images would make this section really great. There are images that help with understanding the content. Try to find information on current treatments and/or management techniques for each disease.

However, some images have no captions and so some seem vague as to what they’re about. There are a few images missing copyright, specifically the 2nd photo on the project page and the historical image of lung development. From what I know, images from textbooks normally can’t be used because of copyright. The content is cited and referenced correctly. A bit messy with the references right now but I understand why. Just don’t forget to organise it before submission. Also, don’t forget to mention the other sections in the introduction. Overall, this project is done really well. It is very informative and easy to understand. In summary, just a few more images and correction of typos and this project would be remarkable. Well done!

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Firstly, great job on the layout and formatting of the project, everything is easy to find and overall, it reads well. The introduction provides great insight of what to expect on the page. However, it lacks in-text citations for the first three subheadings of the page, as well as the table of lung developmental stages. The first two images also don’t have a description when I click on it, I don’t know what I’m looking at. The “student template” is also missing for the images. 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. Otherwise, the lung developmental stages table is informative and easy to read. I would also recommend adding an image for better visualization of the developmental process.

The historical findings and current research models have very detailed content, and look as though they have been referenced correctly using in-text citations, I’m impressed. Although, I would suggest you leave all the references to the end 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 done well and there are a wide number of abnormalities covered. The detail of the first two is more in depth than the rest, I’m unsure whether they was more information on those particular abnormalities or their still needs to be information added, but I suggest to have the same amount of information on each disease, if possible.
Overall, the project is very informative and presented well. It just need a few minor edits.

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The pages structure is well done, with appropriate use of heading. The introduction explains the general development of the respiratory system, differentiating embryonic, fetal and postnatal time-span. Like division of conducting and respiratory zones with strong general description of each zones components. The referencing of the first three heads content and images was not present though I presume this could be easily resolved. The Development stages table gives is simple yet informative, particularly liked how the stages during the fetal period had more in-depth feature description then the embryonic and postnatal stages.

The Current research and findings section was in-depth with strong explanations and in-text referencing; only part lacking referencing is the Functional unit section. Some sentences should be broken up to avoid excessive use of commas “However, a study conducted…”. There seems to be a picture missing or placed incorrectly for one of the 2013 studies. The Lung Model picture is relevant but with no caption, though the description and referencing when clicking on the image is solid. Little improvement is needed for the Historical findings and Abnormalities sections, great referencing and content. Particularly impressed with the sheer amount of abnormalities presented, with information being sourced from 2-3 references for each abnormality.

To improve further, referencing needs to be added particularly to the introduction, conduction and respiratory zone. The references need to be collected at the bottom of the page instead of after every couple of sections. The removal of the multiple reference subheadings would make the content and page in general easier to navigate. Many of the earlier images should be captioned properly and referenced properly, with missing info like ((Template: Student Image)), description, copyright info. The content of Respiratory and Lung Development Stages could be slightly more in-depth though not too significant of an issue. Overall content is written well, providing information on all the important objectives, only place improvement is properly required is referencing and some formatting.

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The introduction provided good background information about the lungs and its general development, however seemed to lack any further explanation as to what else would be covered on the page (current research, abnormalities). I found most of the sentences to be short and abrupt, and more in the form of statements rather than an explanation. This is the same for the following paragraphs regarding the two zones. I would combine several of the sentences together, and restructure them so that they do not start in the same manner e.g. of the first four sentence in your introduction, three of them begin with the words ‘The respiratory system’, and over half the sentences in the entire paragraph begin with ‘The’. There are a few grammatical errors within the text that should be corrected e.g. ‘till’ of ‘until’, ‘id’ instead of ‘is’. The images used fit well, but there is no caption to explain what they are images of and what they are trying to show. This is also not indicated on the summary of the image, one of which also doesn’t include any copyright information.

The lung development stages were done very well, simplified and tabulated making it very clear. My only concern for this part is that it should be the main part of the project, the area where the development of the lungs is fully explained, yet it is the smallest section of the page. Try to expand on it maybe? Or add a picture or two to enlarge the section?

The current research and findings section seems very thorough, lots of content, good explanations. Very minor problems however; a slight tendency to over use commas in some areas, while not in others. The current models area has not been added to; make sure to fill it in, or will it be scrapped? I have also noticed a picture has been deleted so make sure to get that issue fixed if you still want to use the same image. Is the second picture under this heading part of the section? As it is after the references so I'm not sure where it lies exactly. The image should be captioned as well.

I really like the historical findings section, the information seems more concise when it is presented in bullet points. The second picture within this section is well done and very neatly labeled (I thought it was an image from the internet). The first picture though, needs a caption added as well as copyright information. The abnormalities section is very extensive which can be bother good and bad. For some of the abnormalities there is a lot of detail presented, while for others there is very little. I think maybe that as long as you mention what it is, how you get it/how it forms, some statistics and maybe an image, that should be more than enough. Also, I would remove all the sub-headings under abnormalities and have them just written in bold. Otherwise, when looking at the contents at the top of the page, it looks as though half your page is solely focused on abnormalities.

Overall, I think this page is well done and only a focus on sentence structure, a bit on grammar, and captioning pictures with correct copyright info is needed. Other than these main focus areas, one other point to make would be all the references should be at the bottom of the page.

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In this review I intend to highlight the merits of your project as well as provide some constructive criticism in light of the marking criteria of this task.

The page is well structured and provides perfect balance between written text and images. However some of the included images do not compliment the text. I suggest adding labels or descriptive annotations to these images using paint. Alternatively you could refer to these images in your text e.g “ as seen in Figure 4a” and use them to make the descriptive content easier to visualise. You could also include a simple written description of what each image showing in the image link. I found the table on the stages of lung development a really effective way of organising the content and I was able to understand much of it in a quick glimpse! I like how the text is summarised and highlights the main developmental changes that are occurring at each stage. Just to make it more engaging, perhaps you could include matching images in a another column.

Under the section of current findings, I believe that most of the information included is relevant and incredibly appropriate articles have been selected. I think its good that this section is delving into the area of molecular signalling underlying the morphological changes that we see. I believe your project would greatly benefit if there was more material discussing the biochemical signalling and recent findings in relation to this. However, I am not sure if the details on cell type should be in this section, this section might need some re-organising.

I understand that the history is a difficult topic to research. The information on our understanding of surfactant is appropriate, detailed and very informative. However I think you need to include more information on our understanding of stages in fetal lung development. Explore the transition in research focus investigating morphology to molecular changes. Perhaps use the library database to find relevant historic journal articles in the database. It was good to see the use of relevant historic images.

A number of abnormalities have been identified and described, I think its great that each section includes a description of the abnormality, and goes on to discuss the cause and implications of each disease. I would only recommend including images to make the content easy to visualise. Great Work!

Overall the project is coming along really well ! Just ensure that you proof read and review before the final submission. Also include in-text references and compile all your references to one section at the end of the page. Good Luck!!

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Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming. Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone !

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The intro is very good and the images are a good size but there needs to be some description to make it relevant to the project. Need to edit ‘Conducting Zone’ info since there are some grammatical and spelling errors. Also should have in-text referencing in this section of the project with a long list of all the references at the end. You can go onto other people’s reports to find the coding for this reference style.

The information on the lung development timeline is fantastic but it is a bit dense. Splitting it into bullet points might be a better way of organising it so peers get a more effective learning experience when they read it. In the conducting system under current findings it looks like there has been an attempt to upload an image called “400px” however the link leads nowhere. It has great information, very interesting and concise. However the references at the end of this section should be incorporated at the very end of the wiki page. This would make it flow better.

Excellent images of the diseased lung compared to normal lung, however it might make more sense for these to be under the lung abnormalities subheading. There is excellent information on the historical findings. It has been written in an easy to understand manner and all the information is relevant. There is also excellent referencing and good use of diagrams. However I still think that the references should all be together at the very end of the project page.

The abnormalities section is very in depth however there is a bit too much information. It would be easier to follow and more interesting if there were images associated with the information, or maybe if the information was tabulated that would make it easier to follow. Well done on this project! It is clear that a lot of research has been done outside.

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This is a really good project. First thing noticeable on the page is the amount of information you have which is great. The introduction is really well written and I like the fact that you have included images in this part as it makes it so much easier to understand. I also found it quite easy to grasp the difference in fetal and embryonic periods so well done as this is an important part of the project. This table of the lung development stages is great and really well done.

One thing you could maybe do here is add a few diagrams. I know you have more diagrams down below but I think it’s something that might make it even easier to follow. You obviously haven’t found any current models at the moment. Don’t know if this helps but it may for the models: PMID: 22876201. Current research and findings again is good. Something which seems to be reoccurring with your page is the fact that the references are spread all over the page. I think it would look much better if all the references were at the bottom of the page as this makes you page look more professional and aesthetically pleasing.

Maybe add some student drawings as I think this would more interesting for your page and be a bit more unique. Something else to note is the abnormalities part. It’s great that you have a lot of different abnormalities but I feel as though some of them such as cystic fibrosis and laryngeal atresia could have been given a bit more of information to supplement what you are saying. Also adding a diagram would be good to make it easier for the viewer to understand.

Overall it’s a well presented page with some quality information. Maybe look at your referencing technique, adding some more student images and a bit more detail to the abnormalities to take what at the moment is a good project to a great project. Best of luck!!

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Overall, the project at this stage consists of a good integration of text, images and references throughout. The introduction is well-written and gives an overview of the two parts of the respiratory system (conducting and respiratory zones). I think it is a good idea that your group has split this up and explained both parts separately as it helps to orient an unknowing reader, especially as the gross anatomical structures are also described (e.g. trachea, larynx, bronchi). However, in-text referencing is needed in this introductory segment to provide the reader with the source of all information, exactly where it appears. You could refer to Dr Hill’s instructions on how to do this if needed, or see another group’s page on Edit mode. Also, the images used in the introduction should have a small caption beneath them, otherwise it is hard to tell what the images show exactly and how this may be relevant to the complementary text.

In terms of heading and subheading organisation, I like how you have split the content up into 5 main areas of introduction, lung development stages, current research models/findings, historic findings and abnormalities. This makes the page easy to navigate and the subheadings under each section are relevant. The use of a table in the ‘lung development stages’ section is very well done and appropriate, as it segments the information into a clean, readable format that a student could simply refer to if they were learning from scratch. The information in the table is succinct and provides all the main points. The only improvement here I would suggest, is aligning the content to the left, as it may seem more pleasing to the eye to have even spacing rather than centre alignment. Also, the ‘references’ have been placed as subheading 2.1, whereas the other ‘reference’ sections have not been given a separate subheading, so I would consider making this consistent throughout the project page.

The section on current research models and findings is concise and informative, with good use of numbering to make the information easier to read rather than having long and chunky paragraphs. Although a minor detail, there is one part that says “a study conducted last year”. Since these Wiki pages will be left online, it is important to specify the exact year here, and provide an in-text reference to the study mentioned so a reader can easily locate it. I like the use of dot points in this section, making it look appealing, however the image used should also include a caption, as should the others on the page. Be careful of copyright infringement regarding image use, as there appears to be a file with a ‘Permission Error’ in this section, which may need to be manually removed.

The ‘historic findings’ section was also well-done, especially because it used dot points to segment the information and show the exact years of each discovery. Once again though, the image requires a caption and the references for this section seem to be split into 2 parts; one list from 1-14 then another from 1-4. I think the list from 1-4 needs a subheading to show how those sources are different to the ones above it, otherwise both lists need to be integrated into one.There are also some parts that have coding showing </ol> and </span> </li> which just need to be removed with editing.

Lastly, the section on abnormalities is also of a high standard as each abnormality begins with a brief description then goes into details by using dot points. There is good use of in-text referencing followed by a reference list which is correctly formatted too. The image included has a caption which is good, as other sections lack this, however I would consider adding more images to make this part more visually appealing and engaging to the reader.

It is evident that a lot of work has been done on this page as each section is detailed and referenced well, with relevant information. Maybe just consider adding some student-drawn images too, but otherwise, the project is of very good quality so far.

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Respiratory

The introduction doesn’t seem to be a flowing paragraph, but is a collection of rather short sentences with the topic changing every time and is hard to follow, and some like these “During the embryonic and fetal stage the respiratory system is developing.” seem rather obvious for the target audience of university science students.

The overall layout of the project seem weird as well - putting the current researches, and historic findings before the conducting / respiratory zone seem to make sense. Also the amount of information per section is extremely unbalanced; there is too much abnormalities and hardly sufficient information on the actual development of the lungs. The references are not put together yet either.
The lung development stage graph is really well done, easy to read and is visually appealing. Also maybe add a few photo’s in the abnormalities section just to make it visually appealing; there is a lot of information in there but only has one picture.
There are a few parts with grammatical errors / could use with some better punctuation and wording. For example the first sentence under the 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” could be better reworded as “The conducting zone’s function is to filter, warm and moisten air and conduct it to the lungs, and is made up of the nose, pharynx, trachea and bronchioles” or something along those lines.

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The product was done well overall with lots of information and a good structure. However, I am a bit confused about the sections “respiratory” and “lung development stages”. I guess “lung development stages” is also under “respiratory”, but it seems that they are separated into two big sections.

The introduction clearly explains the development of respiratory system. It is good to divide respiratory tract into 2 main parts and explain them separately. It would be better if it includes a sentence like ‘this website will focus on fetal development of respiratory system.

Using table to explain different stages of lung development is a good idea. It would be easier to read if they are typed in point forms with some images included.

More images could be added under current research, models and findings for easier understanding. Some information should be added under current models.

The historic findings and abnormalities are good and informative.

Some images do not have the information about copyright. It would be better if there is a title for each image included.

In terms of referencing, they are missing in the sections under introduction, conducting zone and respiratory zone. In-text references are also missing in the table about the stages and features of lung development. Also, the images used have not been referenced. Reference list at the end rather than under each section should be used instead.

It is overall a good project and well-researched. More images can be included to balance with the huge amount of text.

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The Introduction of Group 1 is done very well. It is clear, descriptive and very informative. The introduction has been well categorised into categories, with the appropriate choice of labels and subheadings. There is a good choice of pictures and diagrams, which demonstrate a sufficient level research beyond the formal teaching activities. I believe the group could add what they’re page hopes to achieve (outcomes).

The timeline aspect of the group is also well presented. A good choice of histological images would add depth and aid in understanding. The information in this section needs to be referenced correctly.

The current research and findings section is very informative and is referenced excellently. I do believe the layout of this section could be improved, with a better choice of subheadings and clear dates of publication (Its all about recent findings). I believe this section could be summarised further and the picture layout improved to make this section clearer and more succinct. Excellent job nevertheless

The historic section is excellent. It is well referenced, written and explained. It is very informative with an excellent choice of well-described historical images. Particularly enjoyed the timeline on the study of ‘Surfactant’

The abnormalities section has an excellent and varied choice of various abnormalities/diseases. It has an excellent choice of headings and subheadings. The content is also correctly cited and referenced. There is strong evidence of significant scientific research. I do believe the addition of images would further add to the overall understanding of this section. I do believe more information could be added to the ‘Azygos Lobe’, ‘Congenital Laryngeal Webs’ and ‘CHAOS’ section or these sections removed and more content/depth added to the other remaining sections (only a suggestion though!)

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Overall structure of this group project is decent with use of many articles to support information provided. Furthermore, the structure for this project could be improved on as there are minimal grammatical errors. It is also able to explain concepts regarding the development of the respiratory system in the embryonic stages. If concepts can be conveyed effectively to the reader then this indicates that the project group have been able to demonstrate their understanding on their chosen topic. It is important to identify the advantages and disadvantages and these are;

====Strengths====

• Images used are effective in further summarising or explaining content. For example the image under the respiratory zone heading is good in that it shows the histological growth of the tissue as the week’s progress on.

• Heading s provided are short and right to the point.

• The table on lung development stages is very effective as it summarises changes that occur in the weeks following embryonic development.

• Abnormalities section has also been clearly written with in-text citations and a variety of research articles used to explain the conditions.

====Weaknesses====

• First and foremost, most images uploaded onto the group project 1 page do not have any descriptions as well an image name to explain what it is. This makes it difficult for the reader to understand what the image is displaying. Also a file has been deleted (400px) indicating that copyright issues have occurred.

• Consistency across the whole project page is not evident. This can be seen as each section has references being placed under paragraphs and then a full reference list is given in the end. So all references need to be placed in the reference list at the end.

• Historic findings are an important section here that needs work on as there isn’t enough information regarding articles from the 18th century being stated.

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 16:13, 17 August 2014 (EST)
Hey guys, it's Emanuel
I've had a look into the systems and respiratory caught my interest. I wanted to do cardio but another group has already chosen it so I think we should choose a system ASAP.

Respiratory looks like it has plenty of resources and there are some interesting abnormalities gat I found on this page:
[http://embryology.med.unsw.edu.au/embryology/index.php?title=Respiratory_System_-_Abnormalities Respiratory Abnormalities]

Do you guys have any other systems you would like to do or do you like respiratory?

--[[User:Z3372817|Z3372817]] ([[User talk:Z3372817|talk]]) 20:07, 17 August 2014 (EST)
Hey Emanuel, its Ish here.

As we said on the day, we're fine with anything. So if it's still free, let's lock it in before another group claims it?

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 20:59, 17 August 2014 (EST) Alright awesome, well I guess we're the Respiratory group. How do we let Dr Hill know?

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 22:30, 17 August 2014 (EST) Hi guys, it's Nadine. I'm happy to do the respiratory system :) I'm sure we have to email him, I'll do that now, since we all seem to be on the same page and in agreement with the respiratory system.

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 22:56, 17 August 2014 (EST) Just emailed Dr Mark and put a heading "respiratory" on our group page :)
Also we each need to pick one of the following;
# 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 fetal period.
I'm happy to do number 1. Unless someone else wants to?

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 06:09, 18 August 2014 (EST)Thanks Nadine, I'll do number 4 if that's all good with you guys?

--[[User:Z3372817|Z3372817]] ([[User talk:Z3372817|talk]]) 19:54, 18 August 2014 (EST) Great work with allocating Nadine. I'd love to do the historic findings (number 3) that sounds interesting! Only if that's okay with you all though?

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 15:17, 19 August 2014 (EST) Hey Guys! It's marina here :), I'm happy with number 2. If anyone comes across information for other parts of the project, let's let each other know :)

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 21:07, 26 August 2014 (EST)Hi guys its Nadine, just wanted to let you guys know that i added in subheadings to our page :) So feel free to add to your sections -pictures -articles -tables

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 23:58, 26 August 2014 (EST)Marina: Thanks Nadine :) I'm just going to add our names next to each section that we are looking at so its easier to communicate with with one another and who's doing what :)

# Review that system development during the fetal period-Nadine
# Identify current research models and finding-Marina
# Identify historic findings-Ish
# Identify abnormalities that can occur in this system during fetal period-Emanuel

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:58, 27 August 2014 (EST)
'''Topics to cover'''
#Major stages of development - all fetal (only primordial embryonic development)
#Histological findings
#Separate into Functional elements (alveoli) and Tract (conducting system: upper and lower)
#Include diaphragm (musculoskeletal)
#Changes after birth

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:20, 2 September 2014 (EST) Emanuel: Hey guys just letting you know that I spoke to Dr Hill before the lecture with Carl from the cardio group about using review articles. He said we are allowed to use them as long as we refer to them appropriately (e.g as reviewed in..., according to review by..., etc).
He also said that any direct findings need to be referenced from the original article and not a review article.
We can reference to them as mentioned above and we can also add a subheading under references titled "review articles" if we want. When we start to formulate the page we can look at what previous projects have done when organising their review article references for ideas.
In regards to using images from review articles - there is no need to cite them as coming from review article.

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 15:41, 2 September 2014 (EST) Emanuel: Hey guys just looking through the lecture and I noticed the part about the development of the pharynx. It develops with the foregut (oesophagus) of the GIT. What do you think if Nadine mentions that groups page in an appendix for her section to link the two pages? There is also a relationship between the development of the liver in wk7 that stops the descent of the heart and lungs so it could make our project more interesting in that it links out page with others offering a wider scope of information along with our specific topic.

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 11:37, 3 September 2014 (EST)Marina: Yeh I agree! I noticed that too Emanuel. The development of the oesophagus from the foregut and how it bifurcated from the common pharynx into the trachea is very much related to our topic. We can definitely include those relationships, and any others we come across

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 22:47, 9 September 2014 (EST) Emanuel: Hey Ish, just came across these articles regarding historical findings for pulmonary surfactant:

[http://www.ncbi.nlm.nih.gov/pubmed/18446178 Surfactants: past, preset and future.]

[http://www.ncbi.nlm.nih.gov/pubmed/14509914 The era of pulmonary surfactant from Laplace to nowadays]

Mary Ellen Avery and Jere Mead seem to be the godparents of surfactant discovery.
I also noticed that there is a little tool on the right hand side of the pubmed page when you search for articles called "Results by year". It's a little bar graph showing which years had the most articles and you can click on each year to bring up it's articles. This might be helpful if your looking for articles that sparked an increase in research by clicking on the years just before the spikes in articles.

--[[User:Z3372817|Z3372817]] ([[User talk:Z3372817|talk]]) 15:49, 16 September 2014 (EST) That is just amazing Emanuel, thanks! Just another thing I wanted to ask, I noticed you took notes when Mark came by to talk to our group at the last lab. When he was saying to focus on things like..
Yeah, do you mind just typing up what you had written. That would be so helpful!

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 23:33, 16 September 2014 (EST)Marina: Hey guys, just uploaded an image onto our page. It's under current research because its something scientists are looking at the moment with tracking abnormalities. The picture compares the normal structure of a lung to a couple of diseased ones. I know this also links to other parts of our project so we can shift it around later if need be. Mark wanted a picture uploaded before tomorrow, so at least we have something up there for now :)

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 12:13, 17 September 2014 (EST) Nadine here, just wanted to inform you that we have a new group assessment that will be marked individually we need to pick 2-3 research papers on stem biology and we need to summarize the paper and present it in week 12 as a group. You will get an email in regards to this set assignment, just thought I'd give you a head up.

--[[User:Z3333429|Z3333429]] ([[User talk:Z3333429|talk]]) 12:44, 17 September 2014 (EST) Emanuel: This is for Ish, I found a link on the respiratory pages that should help you out. Just go to one of the pages (e.g Respiratory System - Abnormalities) and there is a 'Historic Embryology' link just after the introduction. It's small and in a blue box so click on it to expand. It has some really good links that will hopefully help you. Something else that was interesting was the disclaimer at the bottom of the links stressing that the content and scientific understanding are specific to the time of publication. You may want to ask Dr Hill if you need to include that at the bottom of the page to make sure that our audience does not get confused.

--[[User:Z3372817|Z3372817]] ([[User talk:Z3372817|talk]]) 13:27, 17 September 2014 (EST) Ish: Yup, I've seen that Emanuel. I sort of wrote a paragraph along those lines as an introduction to my section which serves as a type of disclaimer too, but I'll reconfirm with Mark whether it's necessary to have anything in addition to that. Nadine, thanks for the heads up.

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 16:21, 1 October 2014 (EST) Nadine: Hey guys, just wanted to remind you that by the end of this week all information should up for your section. Make sure that references are included, pictures if needed.

--[[User:Z3372817|Z3372817]] ([[User talk:Z3372817|talk]]) 20:34, 1 October 2014 (EST) Ish: Hey guys, anyone else having issues with the website lately? I'm trying to upload an image - can't. I completed my latest lab assessment a couple days ago and saved it - lost it. So just to be safe, once you've written everything you need down in your sections, copy and paste EVERYTHING into a separate word doc. Don't want you guys to lose hours of work like I did.

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 19:02, 3 October 2014 (EST) Marina: Hey Ish yeh im also having trouble with it as well. Even the "uploading image" button is inactive for me, apparently others are having as few problems with this as well. Can you guys check if you yours is visible at the moment? I know this must be recent as you guys have uploaded images and i was able to before. Maybe it has to do with the website change Dr Mark was talking about.

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 21:10, 4 October 2014 (EST) Nadine: Thanks Ish! i had the same problem happened twice to me! But it worked out for me in the end. So i have been looking around -projects from years before us and i really like this layout. Have a look if you get the chance [https://embryology.med.unsw.edu.au/embryology/index.php/2012_Group_Project_3]

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 22:50, 4 October 2014 (EST) Marina: Hey Nardine, i really like that layout, hopefully we can get something similar to that going for us as well :) I'm sorry I havent been able to upload any images as the tab for me is unavailable, i emailed Dr mark about it though so hopefully that gets fixed soon.

--[[User:Z3332339|Z3332339]] ([[User talk:Z3332339|talk]]) 22:51, 4 October 2014 (EST) Marina: I was thinking of adding a heading titled "Glossary" at the very end of our project for us to add any words we want to define.... what do you guys think of this?

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 20:33, 7 October 2014 (EST) Nadine: Hey Marina, i like that idea heaps and i was also thinking of drawing for my section i found a great paper with fantastic pictures but i cant find the copyright information its off Nature, or I'll just figure something out

--[[User:Z3330991|Z3330991]] ([[User talk:Z3330991|talk]]) 20:36, 7 October 2014 (EST) Nadine: Hey I was thinking we need to get on top of the week 12 project maybe we can talk about this further tomorrow? I just dont want all of the good papers to go fast and we get left with really hard ones.

Talk:2014 Group Project 3

2014-10-14T14:12:01Z

Z3463310: /* 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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 ☺

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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.

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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!!

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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.

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--[[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>

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*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

Talk:2014 Group Project 4

2014-10-14T14:11:00Z

Z3463310: /* 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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!!

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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.

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==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

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*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

Talk:2014 Group Project 5

2014-10-14T14:03:33Z

Z3463310: /* 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!

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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.

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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.

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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.

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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!

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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!

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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.

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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.

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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.

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*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

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==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 6

2014-10-14T14:01:45Z

Z3463310: /* 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.

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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.

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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!

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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.

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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).

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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.

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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.

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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!

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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 ☺.

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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!

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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!

== 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 =]

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*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 7

2014-10-14T13:58:39Z

Z3463310: /* 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!

--[[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

2014-10-14T13:54:21Z

Z3463310: /* 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!

==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

2014 Group Project 2

2014-10-08T01:58:24Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> [[image:Urethra-bladder.jpg|top|right]]

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme resulting in the formation of the metanephros and its collecting system <ref name=”PMID24439109”><pubmed>24439109</pubmed></ref>

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>
<pubmed>24439109</pubmed>
===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

File:Urethra-bladder.jpg

2014-10-08T01:46:27Z

Z3463310: diagram of urethra / bladder of a human. NIDDK. (2010). National Kidney and Urologic Diseases. Retrieved October 7, 2014, from U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES: http://kidney.niddk.nih.gov/kudiseases/pubs/udictionary/pages/A_D.aspx Copyri...

diagram of urethra / bladder of a human.

NIDDK. (2010). National Kidney and Urologic Diseases. Retrieved October 7, 2014, from U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES: http://kidney.niddk.nih.gov/kudiseases/pubs/udictionary/pages/A_D.aspx

Copyright:
The majority of information at this site is in the public domain. Unless stated otherwise, documents and files on NIH web servers can be freely downloaded and reproduced. Most documents on this server are sponsored by the NIH; however, you may encounter documents that were sponsored along with private companies and other organizations. Accordingly, other parties may retain all rights to publish or reproduce these documents or to allow others to do so. Some documents available from this server may be protected under the United States and foreign copyright laws. Permission to reproduce may be required...

2014 Group Project 2

2014-10-08T01:26:13Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-08T01:22:12Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref>

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-08T01:18:15Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref>

===references===
<references/>

==Urine Formation during the fetal period==

The amniotic fluid is mainly composed of nutrients that will supply the fetus, and its components fluctuate during pregnancy according to the fetal development. [5]
As the fetus develops, it excretes fetal urine into the amniotic sac.

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore] [5]

Sebe. P., Schwentner. C., Oswald. J., Radmayr. C., Bartsch. G., Fritsch. H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15389795 [1]]

Werff. V. D., Nievelstein. R.A, Brands. E., Luijsterburg. A.J., Vermeij-Keers. C. Normal development of the male anterior urethra. Teratology (2005) [http://www.ncbi.nlm.nih.gov/pubmed/10661906 [2]]

Sebe. P., Fritsch. H., Oswald. J., Schwentner. C., Lunacek. A., Bartsch. G., Radmayr. C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J urol (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15821572 [3]]

Ludwikowski B, Hayward OI, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8. [http://www.ncbi.nlm.nih.gov/pubmed/11298059 [4]]

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-08T01:14:04Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

The urethral sphincter complex is important in controlling urination frequency and timing, and is histologically identifiable within the urogenital sinus from week 9 of development as a mesenchymal condensation after the cloacal division. It develops into an inner layer of smooth muscle fibres and outer layer of striated muscle layers by week 15 of development, which further develop into an omega shaped muscle apparatus surrounding the urethra. The urethral sphincter complex muscles are innervated by autonomic and somatic nervous systems, and correct development of the muscle nerve innervation and the urethral sphincters are essential in the maintenance of normal urinary continence post natally. <ref><pubmed>23408557</pubmed></ref>

===references===
<references/>

==Urine Formation during the fetal period==

The amniotic fluid is mainly composed of nutrients that will supply the fetus, and its components fluctuate during pregnancy according to the fetal development. [5]
As the fetus develops, it excretes fetal urine into the amniotic sac.

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore] [5]

Sebe. P., Schwentner. C., Oswald. J., Radmayr. C., Bartsch. G., Fritsch. H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15389795 [1]]

Werff. V. D., Nievelstein. R.A, Brands. E., Luijsterburg. A.J., Vermeij-Keers. C. Normal development of the male anterior urethra. Teratology (2005) [http://www.ncbi.nlm.nih.gov/pubmed/10661906 [2]]

Sebe. P., Fritsch. H., Oswald. J., Schwentner. C., Lunacek. A., Bartsch. G., Radmayr. C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J urol (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15821572 [3]]

Ludwikowski B, Hayward OI, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8. [http://www.ncbi.nlm.nih.gov/pubmed/11298059 [4]]

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

Renal agenesis is typically associated with other congenital defects, including:
* Oligohydraminos
* Facial abnormalities including: wide set eyes, a recessed chin and low-set ears

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-08T01:05:38Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

===references===
<references/>

==Urine Formation during the fetal period==

The amniotic fluid is mainly composed of nutrients that will supply the fetus, and its components fluctuate during pregnancy according to the fetal development. [5]
As the fetus develops, it excretes fetal urine into the amniotic sac.

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore] [5]

Sebe. P., Schwentner. C., Oswald. J., Radmayr. C., Bartsch. G., Fritsch. H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15389795 [1]]

Werff. V. D., Nievelstein. R.A, Brands. E., Luijsterburg. A.J., Vermeij-Keers. C. Normal development of the male anterior urethra. Teratology (2005) [http://www.ncbi.nlm.nih.gov/pubmed/10661906 [2]]

Sebe. P., Fritsch. H., Oswald. J., Schwentner. C., Lunacek. A., Bartsch. G., Radmayr. C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J urol (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15821572 [3]]

Ludwikowski B, Hayward OI, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8. [http://www.ncbi.nlm.nih.gov/pubmed/11298059 [4]]

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

2014 Group Project 2

2014-10-08T00:57:51Z

Z3463310: /* Urethra */

{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 11-12 - degeneration of the mesonephri

Week 36 – nephrogenesis is complete, however can occur as early as week 32

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One recent research paper buy Al-Odat et al. used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood. <ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children; therefore it is important to find a way to prevent the damages to the renal system caused by the obstruction.
A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

==Kidney==

===Early Development===
[[File:Development of Kidney.jpg|300px|thumb|The development of the kidney from epithelial origin to fully formed]]The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref><pubmed>24656820</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref><pubmed>25088264</pubmed></ref>

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed for the continued nephrogenesis, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further maturation of the glomeruli post-natally before the kidneys are fully functional.

'''Nephrogenesis'''

The formation of nephrons continues well after the embryonic period in concert with the branching of the ureteric bud <ref><pubmed>24656820</pubmed></ref>, ending between week 32-36 of gestation <ref><pubmed>24488483</pubmed></ref>. It is during this period that the self-renewing process of the progenitor cells ceases and they differentiate into nephrons for the final time <ref><pubmed>24656820</pubmed></ref>. The process of nephron formation is shown in the second diagram to the right <ref><pubmed>24011574</pubmed></ref>. [[File:Nephron Maturation.jpg|300px|thumb| (A) The mesenchymal cells interact with the ureteric bud, causing branching of this structure to occur (B). Renal vesicles are also formed at these branch points which then fuse to the ureteric stalk (C), creating S-shaped bodies. (D) Glomerular development occurs as this structure continues to develop, forming a nephron.]]
Although nephrogenesis is terminated by week 36, the resulting kidney is not yet fully functional. At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born <ref><pubmed>24781774</pubmed></ref>. This maturation phase due to postnatal adaption to extrauterine life occurs during early infancy <ref><pubmed>24623338</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count <ref><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies <ref><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth <ref><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process <ref><pubmed>24022365</pubmed></ref>.

'''Genes'''

While there are many genes and transcription factors that regulate the formation of early kidney development, the main factor that continues to be expressed as the fetal kidney develops is the Gremlin gene. The gene, coded GREM1, has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When the kidney is fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene <ref><pubmed>25036148</pubmed></ref>.
[[Image:The kidney of a FA-injected mouse compared to a wildtype mouse.jpg|300px|thumb| The morphology of the kidney when Gremlin is expressed at normal levels (left), compared to when the gene is over-expressed (right).]]

'''Anatomical Position'''

The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect (Keeling & Khong, 2007; Moore, 2011).

During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys (Keeling & Khong, 2007).

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623

Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

'''Renin Production'''

While the kidneys develop, particularly the tubules, the production of renin can be found within these areas. As the tubular activity increases and this component proliferates in number and size, it is noted that growth is proportional to the amount of renin produced; as growth and functional state of the tubules increase, so does the concentration of renin created <ref><pubmed>19871238</pubmed></ref>.

==Urethra==

The urethra is a structure that allows for excretion of urine, and presents as a tube from the urinary bladder to the external urethral orifice. The urethra originally develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus (endoderm), and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref>

External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

The anterior part of the urogenital sinus (develops into the bladder) has an opening at the apex which is connected to the allantois during fetal development. The function of this opening at the apex of the fetal bladder is to drain the developing bladder to the allantois via the umbilical cord. At around week 15 of fetal life, the allantois regresses and becomes known as the urachus; at which time the vesicourethral canal develops into the pelvic segment of the urethra in the male fetus, and the entire urethra in the female fetus. The remaining parts of the urogenital sinus (posterior portion) "later develops into the phallic urethra in the male and the lower portion of the vagina and vaginal vestibule with perineal urethra orifice in the female." (Hila Milo Rasouly, Weining Lu. 2013) <ref><pubmed>23408557</pubmed></ref>

==Urine Formation during the fetal period==

The amniotic fluid is mainly composed of nutrients that will supply the fetus, and its components fluctuate during pregnancy according to the fetal development. [5]
As the fetus develops, it excretes fetal urine into the amniotic sac.

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore] [5]

Sebe. P., Schwentner. C., Oswald. J., Radmayr. C., Bartsch. G., Fritsch. H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15389795 [1]]

Werff. V. D., Nievelstein. R.A, Brands. E., Luijsterburg. A.J., Vermeij-Keers. C. Normal development of the male anterior urethra. Teratology (2005) [http://www.ncbi.nlm.nih.gov/pubmed/10661906 [2]]

Sebe. P., Fritsch. H., Oswald. J., Schwentner. C., Lunacek. A., Bartsch. G., Radmayr. C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J urol (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15821572 [3]]

Ludwikowski B, Hayward OI, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8. [http://www.ncbi.nlm.nih.gov/pubmed/11298059 [4]]

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys before it is excreted via the urethra <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the bladder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder <ref name="PMID23371862"><pubmed>23371862</pubmed></ref>. The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine this is not a problem for the embryo as urine is released directly into the amniotic cavity <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>. The muscles in the bladder however are very important for normal urine output once the foetus have been delivered; as development continues the walls of the bladder muscle thicken and there is a decrease in collagen content, this increases the compliance of the bladder <ref name="PMID2621133"><pubmed>2621133</pubmed></ref>.

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder <ref name="PMID22535797"><pubmed>22535797</pubmed></ref>.It also could be due to the increasing number of nerves in the detrusor muscle during foetal development, this would lead to an increase control over the bladder wall due to the increase in nerves present <ref name="PMID3627353"><pubmed>3627353</pubmed></ref>.

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. Unilateral renal agenesis has a frequency of 1 in 5,000 newborns, in contrast to bilateral renal agenesis the rarer of the two, occurring in 1 in 30,000 infants <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>.

Induction of the ureteric bud from the nephric duct is mediated by glia cell-derived neurotrophic factor (GDNF), which is secreted by the metanephric mesenchyme and interacts with the tyrosine kinase c-Ret receptor expressed in the ureteric bud in order to induce branching of the nephric duct <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>
In animal models, renal agenesis is linked to signalling failures failure of the GDNF–RET signalling <ref name=”PMID18252215”><pubmed>18252215</pubmed></ref>. A complex molecular network that includes regulation by EYA1, the sine oculis homeobox homologues SIX1 and SIX4, and PAX2, controls the activation of GDNF in the metanephric mesenchyme. In addition, members of the HOX11 paralogous genes13 and the signalling molecule growth and differentiation factor 11 (GDF11) 14 are required for GDNF signals that are derived from sources other than the metanephric mesenchyme (for example, the developing gut) are not interpreted in more rostral parts of the embryo. Although Mutations in GDNF or RET have yet to be linked with mutations in patients with kidney defects such as renal agenesis. A possible explanation for this could be because human kidney development is not susceptible to the slight reduction in protein level that results from heterozygous inactivation. <ref name=”PMID17878895”><pubmed>17878895</pubmed></ref>

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===
[[File:PKD.jpg|400px|thumb|Cyst formation at the level of the cell, nephron, and kidney]]

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<pubmed>16932388</pubmed>
<pubmed>17878895</pubmed>
<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

==References==
<references/>

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2014 Group Project 2

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{{ANAT2341Project2014header}}
=Renal=
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 15:11, 26 August 2014 (EST) No subheadings yet and I even had to add your project title! Get moving.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:00, 6 September 2014 (EST) OK some sub-headings and a few refs. No content yet expelling the feral component or how the references you have selected relate to the topic.

==Introduction==

The renal system's main function is the production, storage and elimination of urine, and to maintain the balance of chemicals and water of the body. Kidneys are the primary organ of the renal system, and consist of smaller units known as nephrons - which filter the blood to remove urea and other wastes, and reabsorb or excrete excess water according to the needs of the body as directed by hormones released by the pituitary glands. Nephrons are made up of glomeruli to filter the blood, tubules to reabsorb any solutes or fluids, and more tubule networks to carry the urine to the bladder and outside the body. Small amounts of urine is released from the kidneys every 1 ~ 15 seconds into the ureter, which carry the urine to the bladder.<ref>Kim Ann Zimmermann (2013). “Urinary System: Facts, Functions & Diseases” Feb 11 2013 </ref> The bladder is a hollow organ which has the ability to change its epithelium according to how full the bladder is of urine. "The bladder's walls relax and expand to store urine, and contract and flatten to empty urine through the urethra. The typical healthy adult bladder can store up to two cups of urine for two to five hours.”<ref> Stanford (2014). “Anatomy of the urinary system” </ref> Two sphincter muscles are present at the base of the bladder, and two more at the end of the urethra (internal & external) to voluntarily control the excretion of urine.

Development of these components begin during the embryonic phase, and continue to develop and mature throughout the fetal stages. During the fetal stages, some abnormalities may form. During the embryonic period and fetal periods, the mother's placenta work to remove wastes from the fetus.

Abnormalities may arise during the embryonic and fetal stages of development of the renal system, such as Hereditary renal adysplasia, or polycystic kidney disease. Hereditary renal adysplasia is an inherited condition, where there is malformations in organs derived of the embryonic mesoderm.<ref><pubmed>20388228</pubmed></ref> Polycystic kidney disease is a fairly common genetic disorder in which fluid-filled cysts displace normal renal tubules.<ref><pubmed>21079243</pubmed></ref>

===references===
<references/>

==Historic findings==

==Developmental Timeline==
Week 3 – nephrogenesis begins, pronephri form

Week ~4 - embryonic development of ureter begins from the ureteric bud

Week 5 – metanephros forms

Week 8 – mature kidney is formed

Week ~10 - Kidneys begin to produce urine

Week 36 – nephrogenesis is complete

Postnatal – maturation of neonatal glomerular filtration

==Current research models==

Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.

One research paper that has recently come out that used mice in order to determine the impact of maternal cigarette smoke exposure on the development of the renal system, in particular kidneys. It was proposed that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life. The experiment found that some fibroblast growth factors were up-regulated whilst others were down-regulated and this led to delayed nephron development and fewer nephrons present at birth. The study showed by using an animal model that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood.

<pubmed>25058584</pubmed>

==Kidney==

===Early Development===
The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros<ref name=”PMID24855634”><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch<ref name=”PMID24656820”><pubmed>24656820</pubmed></ref>.

While it is not well known the mechanisms by which nephron number is determined, the causes of several disorders and diseases, such as renal disease and hypertension, have been attributed to a low nephron count<ref name=”PMID24656820”><pubmed>24656820</pubmed></ref>. It has been determined that a decrease in the number of progenitor cells, a possible result of genetic abnormalities, toxic insults, and nutritional deficiencies<ref name=”PMID24488483”><pubmed>24488483</pubmed></ref>, can result in fewer branching of the ureteric buds, leading to impaired kidney growth<ref name=”PMID24656820”><pubmed>24656820</pubmed></ref>. Therefore, nephron number is important as it can show the success/extent of nephrogenesis, and thus be used to determine if any and what genes and environmental factors may aid this process<ref name=”PMID24022365”><pubmed>24022365</pubmed></ref>.

When sufficient development has occurred during week 3 of gestation, two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. As the pronephri continue to develop, they elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. Towards the bottom of this duct, close to where it connects to the cloaca, is the ureteric bud connected by the ureter. Surrounding this bud is a mass of metanephric mesoderm (blastema), the two of which react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process begins from as early as week 3 and continues until week 8 of gestation. The development of the nephrons however, continue through to week 32-36 of gestation.<ref name=”PMID25088264”><pubmed>25088264</pubmed></ref>

''A drawing of the following picture will be made and uploaded as a direct copy is prohibited under copyright. It shows the formation of the kidney during the embryonic development:http://renalsystem.weebly.com/uploads/1/4/9/9/14997296/9282501_orig.jpg?1''

===Fetal Development===
There are a number of factors that occur in regards to the kidneys during the fetal period of development, the most important of which is the continued generation of nephrons. There are specific genes expressed as well as hormones released for their generation, with vasculature created to supply the newly formed kidneys. There are certain events that occur for the kidneys to achieve their correct anatomical position before they are fully formed, as well as further growth post-natally before the kidneys are fully matured.

An embryonic gene named gremlin (GREM1) has been found to play a key role in the formation of the kidneys and nephrogenesis in general. When fully formed, the expression of this gene is relatively low in an adult. However, it is thought that many renal diseases and their progressions are linked to an overexpression of this gremlin gene.

<pubmed>25036148</pubmed>

At birth, although the infant’s kidneys are developed enough to maintain homeostasis and are sufficient for growth and development, their functional capabilities are decreased. This is a result of the transition from depending on the placenta to maintain homeostasis of fluid and electrolyte balance while in-utero, to maturation of the neonatal glomeruli once born.

<pubmed>24781774</pubmed>

<pubmed>24623338</pubmed>

<pubmed>24011574</pubmed>

<pubmed>19726549</pubmed>

===References===
<references/>

==Urethra==

The urethra develops from the cloaca during fetal development. The cloaca can be divided into the anorectal canal (dorsally) and the urogential sinus (ventrally). The bladder develops from the superior portion of this urogenital sinus, and the inferior portion develops into the urethra. The endoderm of the urogenital sinus derives the urethral epithelium, and the splanchnic mesenchyme develop into the connective tissue and smooth muscle components of the urethra.<ref>Schoenwolf: Larsen's human embryology, 4th ed. chapter 15</ref> External urethral sphincters are thought to develop within week 10 of development. <ref>Ludwikowski B, Oesch Hayward I, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8.</ref>

===References===
<references/>

==Urine Formation during the fetal period==

The amniotic fluid is mainly composed of nutrients that will supply the fetus, and its components fluctuate during pregnancy according to the fetal development. [5]
As the fetus develops, it excretes fetal urine into the amniotic sac.

[http://reference.medscape.com/article/975821-overview Polyhydramnios and oligohydramnios]

[http://www.nature.com/jp/journal/v25/n5/full/7211290a.html amniotic fluid: not just urine anymore] [5]

Sebe. P., Schwentner. C., Oswald. J., Radmayr. C., Bartsch. G., Fritsch. H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15389795 [1]]

Werff. V. D., Nievelstein. R.A, Brands. E., Luijsterburg. A.J., Vermeij-Keers. C. Normal development of the male anterior urethra. Teratology (2005) [http://www.ncbi.nlm.nih.gov/pubmed/10661906 [2]]

Sebe. P., Fritsch. H., Oswald. J., Schwentner. C., Lunacek. A., Bartsch. G., Radmayr. C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J urol (2005) [http://www.ncbi.nlm.nih.gov/pubmed/15821572 [3]]

Ludwikowski B, Hayward OI, Brenner E, Fritsch H. The development of the external urethral sphincter in humans. BJU Int. 2001 Apr;87(6):565-8. [http://www.ncbi.nlm.nih.gov/pubmed/11298059 [4]]

==Kidney Anatomical Position==

Kidneys initially begin to develop proximally to the pelvis, located ventrally to the sacrum. As the fetus develops, the kidneys must move to attain their adult anatomical positions which is towards the dorsal sides of the body at around T12~L3 levels. This process is usually completed by week 9 of fetal development, and result mainly from the kidneys coming in contact to the supra-adrenal glands, and also from the growth in size of the embryo’s body and the abdominal cavity. Medial rotation of the kidneys by up to ninety degrees, and the blood supply to the kidneys from more superior parts of the abdominal aorta (branches begin initially near the common iliac arteries, and receive blood from new branches higher up from the aorta) both contribute to the ascending of the fetal kidneys. [1]

[[Image:Kidney ascent.jpg|600px|kidney ascent diagram]]

[1] Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier

==Ureter==

The development of the ureter typically begins during week 4 of gestation. The process begins from the ureteric bud, which arises from the caudal region of the mesonephric ducts (also known as Wolffian ducts) that run along the edge of the intermediate mesoderm and grows into the adjacent metanephric mesenchyme.

<pubmed>23123402</pubmed>
<pubmed>23408557</pubmed>

===Duplicated Ureter===
<pubmed>24469670</pubmed>
<pubmed>25010444</pubmed>

==Bladder==

The role of the urinary balder in the renal system is to store urine produced by the kidneys and transported in the ureter before it is excreted via the urethra. A flexible epithelium is essential for the bladder as it changes volume by contracting and relaxing depending on the volume of urine in the body.
A fusion event occurs between the common urogenital sinus and the mesonephric duct, this divides the rectal components from the urine components and it allows the balder to develop.

The urinary bladder develops in the first 12 weeks of gestation from the urogenital sinus and the surrounding splanchnic mesenchyme, these development events are controlled by by complex epithelial–mesenchymal signals. The vesical part of the urogenital sinus is attached to the allantois and goes on to form the bladder. (23371862) The lamina propria, the muscle coat and the adventitia all develop from the splanchmic mesoderm whilst the epithelial lining is derived from the endoderm of the urogenital sinus. (Newman)

During foetal development the bladder is supplied by an increasing number of nerves in the detrusor muscle, as the gestational period continues different peptide containing nerves are observed.

<pubmed>23371862</pubmed>

During development the bladder only produces immature reflexes rather than the voluntary bladder control that is only seen once the infant is toilet trained. It is suggested that the switch between involuntary reflexes and voluntary contractions is due to the development of the central and peripheral neural pathways that control the contraction of the bladder.

<pubmed>22535797</pubmed>

Initially the epithelium lining of the urinary bladder is made from two distinct cell layers, the superficial layer and the basal layer. Up to week 11 the rest of the balder wall consists of mesenchyme that gradually matures into lose connective tissue. At the 13th week collagen begins to appear, by the 14th week it is abundant in the lamina propria and by week 15 it has extended into the superficial muscle bundles. Smooth muscle cells begin to appear in the connective tissue during week 12, they initially appear in the proximal part of the organ but they spread distally over time. At 21 weeks the epithelium is 3-4 layers thick, the superficial layer, the intermediate layer, lamina propria and the basal lamina. This epithelium is specialised and contains features that are characteristic of urothelial differentiation so that urine is unable to pass through the bladder wall.
The muscular coat of the bladder does not develop until after the kidneys have begun to produce urine but as the urine is released into the amniotic cavity this is not a problem for the foetus. (Newman)

<pubmed>2621133</pubmed>

<pubmed>23408557</pubmed>

==Abnormalities==
[[File:MRI_renal_agenesis_.jpg|thumb|MRI showing renal agenesis]]
===Renal agenesis===

Renal agenesis is a congenital abnormality referring to the failure of the development of the kidneys and ureter produced by a lack of interaction between the ureteric bud and the metanephric mesenchyme. Renal agenesis can occur in two forms, infants can be born with either bilateral or unilateral renal agenesis. Infants born with bilateral renal agenesis are incompatible with life and are born usually stillborn, or die within a few days after birth <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

<references/>

<pubmed>20798957</pubmed>
<pubmed>24439109</pubmed>
<pubmed>18252215</pubmed>

===Polycystic Kidney Disease===

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the formation of fluid filled cysts in the kidneys, which displace normal renal tubules. There are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

PKD affects approximately 1 in 1000 individuals, with ADPKD accounting for the majority of the cases reported<ref name=”PMID21079243”><pubmed>21079243</pubmed></ref> <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>. ADPKD, also known as adult-onset polycystic kidney disease is commonly reported to present in adulthood in association with hypertension and renal failure <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>. The disease is linked to the mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. These mutations ultimately affect multiple signaling pathways, which cause aberrant gene transcription, cell proliferation, and ion secretion, which in turn result in the formation of benign fluid-filled cysts. As cysts balloon out from individual nephrons, their collective effect leads to the displacement of the normal renal parenchyma and the formation of a cyst-filled kidney with reduced functional capacity <ref name=”PMID21079243”><pubmed>21079243</pubmed></ref>. In ADPKD, the growth of renal cysts produces a progressive increase in renal volume and destruction of the parenchyma, leading to terminal chronic renal failure in adulthood <ref name=”PMID23169372”><pubmed>23169372</pubmed></ref>.

ARPKD, however is the rarer form of PKD, affecting approximately 15% of cases. It commonly presents during the second or third trimester of fetal development. Ultrasound images show kidneys that are usually 'bright' or echogenic and are often associated with progressive oligohydramnios <ref name=”PMID11746154”><pubmed>11746154</pubmed></ref>.

<references/>

<pubmed>18728845</pubmed>
<pubmed>25263802</pubmed>
Mutations in SALL4, a transcription factor important in renal development, can result in renal malformations. <pubmed>21258884</pubmed>
<pubmed>25211294</pubmed>
<pubmed>16462154</pubmed>
<pubmed>11458035</pubmed>

===Horseshoe Kidney===
<pubmed>18059107</pubmed>
<pubmed>17593682</pubmed>
<pubmed>10862660</pubmed>

===References===
<pubmed>18631884</pubmed>
<pubmed>20807610</pubmed>
<pubmed>20388228</pubmed>
<pubmed>11746154</pubmed>
<pubmed>25036148</pubmed>

The overexpression of the gremlin gene (GREM1) has been found to be a cause of renal disease.

<pubmed>24500691</pubmed>

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