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=Melanocytes=

==Introduction==
[[File:Melanocyte1.jpg|280px|thumb|Diagram of an epidermal melanocyte and its structures]]

Melanocytes are a type of neural crest-derived cells in the body {{#pmid:20256541|PMID20256541}}, most commonly found in the stratum basale, the bottom layer of the epidermis of the skin, eyes {{#pmid:16704452|PMID16704452}}, and to a lesser known degree, the meninges (membrane around the brain), the heart {{#pmid: 5476812|PMID5476812}} and the inner ear {{#pmid: 17247639|PMID 17247639}}.

Each melanocyte possesses a main cell body, where most of the cellular functions, including the production of melanin take place. They also possess finger-like projections that extend into the surrounding tissue, similar to neurons, called dendrites. Melanin produced within the cell is packaged into granules, before being transported to the surrounding cells via dendrites, which reach in between the surrounding tissue.

Their most commonly known function is the production of melanin, melanogenesis, of which there are two types; eumelanin (black) and pheomelanin (reddish yellow) {{#pmid:2071942|PMID2071942}}, and are responsible for the pigmentation of various parts of the human body including the skin, hair and irises, etc. Melanogenesis has different levels - basal and activated. The basal level of melanogenesis determines an individual's skin colour and is determined by genetics, i.e. a light-skinned individual has low levels of basal melanogenesis. Activated levels of melanogenesis are usually due to external factors, such as exposure to UV-B radiation, resulting in increased levels of melanogenesis {{#pmid: 15748643|PMID 15748643}}, which can be commonly seen as sunburn or tan after long exposure to sunlight. Other cells in the body are able to produce pigment, such as epithelium of the retina, some neurons and adipocytes, but melanocytes are the only cell of neural crest origin that can perform this function.

==History==
Melanocytes were first described and named ‘chromatophores’ by Giosué Sangiovanni in 1819, who identified them in squid <ref>Sangiovanni, G. (1819) Descrizione di un particolare sistema di organi cromoforo espansivo-dermoideo e dei fenomeni che esso produce, scoperto nei molluschi cefaloso. G. Enciclopedico Napoli, 9, 1-13</ref> . The location of pigmentation in the skin was examined by various scientists from the 1600s, and was found to reside in the epidermis. It wasn't until the early 20th century that the dark granules responsible for this pigmentation, nowadays termed melanosomes, were first identified using light microscopy. The origin of melanosome synthesis within the cell was discovered later in the century using electron microscopy: in 1961, Moyer found that stage 1 melanosomes (those containing matrix material, but no melanin), in pigmented retina, originate from the endoplasmic reticulum of epithelial cells. These findings were later confirmed by Turner, who studied melanosomes in goldfish <ref> Moyer, F. H. Electron microscope observations on the origin, development and genetic control of melanin granules in the mouse eye. In: The Structure of the Eye, G. K. Smelser (ed.). New York: Academic Press, 1961, pp. 469–486 </ref> {{#pmid:805261|PMID805261}}.

The idea that melanocytes originate from neural crest cells was first suggested by Ross Granville Harrison in 1910, when writing a paper on the outgrowth of the nerve fibre <ref>Granville Harrison, R. Archiv für Entwicklungsmechanik der Organismen (1910) 30: 15. https://doi.org/10.1007/BF02263801</ref>. This was later proven by DuShane in 1935: He removed sections of neural fold in stage 15 Amphibia punctatum and tigrinum embryos, and observed a lack of pigment in their trunk region. He then placed the neural fold tissue explants in Holtfreter’s solution (a solution designed to facilitate amphibian development), and observed their differentiation into melanocytes <ref>DuShane, Graham P. "An Experimental Study of the Origin of Pigment Cells in Amphibia." Journal of Experimental Zoology 72, no. 1 (1935): 1-31. https://onlinelibrary-wiley-com.wwwproxy1.library.unsw.edu.au/doi/epdf/10.1002/jez.1400720102 </ref>. In an article published in 1963, James Weston describes using tritiated thymidine labelling to track chick embryo neural crest migration in vivo. He identified a dorsolateral stream of neural crest derived melanoblasts (precursors to melanocytes), migrating to enter the ectoderm {{#pmid:14000137|PMID14000137}}.

==Tissue Organ Structure and Function==

===Skin===

Melanocytes are located in the basal layer of the skin epidermis, amongst keratinocytes. Via dendrites, one melanocyte can communicate with around 30-40 keratinocytes. The role of melanocytes is to produce melanosomes - granules containing the pigment melanin, which are then transferred to keratinocytes <ref>Nordlund, J. J., Boissy, R. E., Hearing, V. A., King, R. S., Oetting, W. P., & Ortonne, J. (2007). The Pigmentary System: Physiology and Pathophysiology: Second Edition. Blackwell Publishing: https://onlinelibrary-wiley-com.ezproxy.is.ed.ac.uk/doi/pdf/10.1002/9780470987100</ref>. Melanocytes synthesise two types of melanin: pheomelanin, which is red/yellow; and eumelanin, which is brown/black. These are produced in varying proportions depending on the individual. Paler skinned individuals synthesise more pheomelanin, whilst darker skinned individuals synthesise more eumelanin {{#pmid:2071942|PMID2071942}}.

Mature melanosomes travel from the cell body to the dendrites of the melanocyte, where they are transported to neighbouring keratinocytes. A recent study has shown that melanosome transfer occurs under the following process:
# Melanocyte dendrites release pigment globules that contain clusters of melanosomes into the extracellular space.
# The pigment globules are then phagocytosed by keratinocytes.
# The globule membrane degrades in the keratinocyte cytosol and the melanosomes are released to populate the perinuclear space {{#pmid:22189785|PMID22189785}}.

In the skin, melanin provides photoprotection to keratinocyte nuclear DNA: By aggregating above the nuclei of keratinocytes, it absorbs ultra violet radiation, which would otherwise damage DNA {{#pmid:17314970|PMID17314970}}.

We all have around the same number of melanocytes in our skin epidermis, but the quantity of melanosomes taken up into keratinocytes varies between individuals - this, as well as the pheomelanin-eumelanin ratio, is what causes variation in skin colour. The darkening of skin can occur due to two causes: Ultraviolet irradiation and locally produced α-Melanocyte-stimulating hormone (α-MSH), both of which stimulate melanogenesis {{#pmid:11041369|PMID11041369}}{{#pmid:7984233|PMID7984233}}{{#pmid:2071942|PMID2071942}}.

[[File:Skin_Melanocytes.jpg|600px|centre|thumb|Figure 2: Diagram of the skin epidermis: shows a melanocyte in the basal epithelium. Its dendrites extend into the stratum spinosum, transferring melanosomes to surrounding keratinocytes via the extracellular space. Melanosomes populate the perinuclear space of the keratinocytes, providing photo-protection{{#pmid:24278043|PMID24278043}}.]]

===Hair===

===Ears===
[[File:Stria Vascularis diagram 2.jpeg|250px|thumb|Figure 2: Diagram of the Stria Vascularis, containing the marginal cells, intermediate melanocytes and basal cells. It shows marginal cell extensions intercalating with melanocytes, and the K+ ion channels involved in generating the EP {{#pmid:25663387|PMID25663387}}.]]

Melanocytes are mainly present in the cochlea, vestibular organ and endolymphatic sac.

The cochlea of the inner ear functions as a transducer, by converting sound vibrations to electrical potentials in the auditory nerve via hair cells <ref>Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. The Inner Ear. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10946/</ref>. In the cochlea of humans, melanocytes are found in the vascularised epithelial tissue in the intermediate layer of the stria vascularis and the modiolus, between the marginal and basal cell layers {{#pmid:3070525|PMID3070525}}(Figure 1). During development, marginal layer cuboidal epithelium develops processes which interdigitate with the intermediate melanocytes and basal cells {{#pmid:2612372|PMID2612372}}.Based on studies performed on mice models, it is thought that melanocytes are important for the development of the endocochlear potential (EP), produced by strial cells. Intermediate melanocytes conduct K+, which plays an important role in sound conductance, as it flows from the endolymph into the ciliated epithelial cells of the ear via mechano-electrical channels. This influx of K+ is driven by a combination of the membrane potential of these ciliated epithelial cells, and the EP. A study on guinea pig models showed that blocking the K+ channels of melanocytes produces a lower EP {{#pmid:8951443|PMID8951443}}. This study agrees with evidence showing that mice deficient in cochlea melanocytes have a lower EP, requiring a greater sound stimulus to produce an action potential {{#pmid:7521050|PMID7521050}}.
[[File:Left and Right Cochlea.jpeg|250px|thumb|center|Figure 3: The cochlea of a Wv/Wv viable dominant spotting mutant - a mutation in both alleles encoding c-kit, an essential growth factor for formation, migration, proliferation and differentiation of melanoblasts. The distribution of melanocytes are shown as dots within the Stria Vascularis of the left cochlea {{#pmid:7521050|PMID7521050}}.]]

===Eyes===

Uveal melanocytes contain both eumelanin and pheomelanin. It has been speculated that eumelanin is photoreceptive, whereas pheomelanin is phototoxic. Uveal melanocytes produce growth factors, such as vascular endothelial growth factor that controls blood circulation around the eye, as well as extracellular matrix degrading enzymes. It was found that both of these roles may play a key part in the toxicity of uveal melanocytes. {{#pmid:12537643|PMID12537643}}The uveal tract (iris, ciliary body and choroid) and conjunctiva normally contains melanocytes derived from the neuro-ectodermal neural crest. Peri-orbital soft tissue is also derived from the embryonic neural crest.{{#pmid:24508696|PMID24508696}} On the other hand, pigmented melanocytes (such as those found on the retina) were derived from the neuroepithelium or from different layers of the optic cup. {{#pmid:23529312|PMID23529312}} Uveal melanocytes (like all other melanocytes) differentiate into melanin-producing cells, which in this case determines a person's eye colour, protects the eye from UV radiation {{#pmid:19002157|PMID19002157}} and can mutate to form many ocular diseases that can cause blindness, including age-related macular degeneration. {{#pmid:18346089|PMID18346089}} Melanocytes found in the eye are not able to participate in regeneration unlike epidermal melanocytes. {{#pmid:24789876|PMID24789876}}

[[File:Melanocytes in Eyes of B6 and ep Mice.jpeg|400px|thumb|center|Figure 4. Pigmentation of the anterior segment of the eyes in B6 and ep mice. (A) Sagittal diagram of anterior eye of adult mouse. Tissues containing melanocytes derived from the neural crest were italicised and pigmented cells derived from the neuroepithelium of the optic cup were underlined. (B) Pigmentation of the anterior segment of the eyes of B6 and ep mice. As shown in the upper-left photo, the iris is defined as the part of tunica vascularis beneath the dotted line; ciliary body is defined as the part between solid and dotted lines; choroid/retina is defined as the part above the solid line. The bar indicates 100 mm. (C) Pigmentation of the ciliary body and ciliary storm in postnatal days, adult, and 3 months old. The bar indicates 50 mm.]]

===Heart===
The term ‘cardiac melanocytes’ is used to describe the population of cells found in the human heart that express the melanin-synthesis enzymes. These cardiac melanocytes also resemble the morphology of the melanocytes found at the cutaneous level {{#pmid:25285608|PMID25285608}}.
[[File:Cardiac melanocyte in an embryonic mouse pup.png|400px|thumb|center|Figure 5. A differential interference contrast (DIC) microscopical image of a cardiac melanocyte present in an isolated atrial cell of an embryonic mouse pup. The white arrow indicates the cardiac melanocyte that is found amidst the atrial myocytes that are marked by the yellow arrowheads. {{#pmid:25285608|PMID25285608}} ]]

===Central Nervous System===
[[File:Meninges of the central nervous system.png|250px|thumb|left|A diagram displaying the layers in the skull, including the meninges.]]
Melanocytes can also be found within the Central Nervous System, primarily in the leptomeninges {{#pmid:26635543|PMID26635543}}, which consists of the inner two layers membranes of the meninges, the pia mater and arachnoid mater, which encapsulate the brain and the spinal cord. While its function within the meninges is unknown, they are essential to the health of the meninges, with their removal increasing the risk of aseptic meningitis {{#pmid:6699426|PMID6699426}}. Furthermore, due to its receptivity to the same signalling molecules as neurons, scientists can study diseases afflicting the central nervous system using it as a model {{#pmid:22158549|PMID22158549}}.

==Embryonic Origins==
As mentioned earlier, melanocytes originate from the pluripotent cells in the neural crest {{#pmid:20256541|PMID20256541}}. After formation of the neural tube, neural crest cells eventually form four different functional domains, namely the cranial neural crest, trunk neural crest, vagal and sacral neural crest, and the cardiac neural crest <ref>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/ </ref>. Melanocytes are descended from melanoblasts, which in turn are formed from trunk neural crest cells migrating along the dorsolateral pathway into the ectoderm via minute holes in the basal lamina <ref>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/ </ref>. These eventually form part of the ears, eyes, skin and leptomeninges, therefore explaining the presence of melanin in these parts as a result of the development of melanoblast subpopulations during early migration {{#pmid:16291526 |PMID16291526}}.

===Cochlear melanocytes of the inner ear===

These melanocytes have recently been found to originate from neural crest cells delaminating from the rhombomere 6 region of the hindbrain, where the glossopharyngeal nerve and third pharyngeal arch are located {{#pmid:25663387|PMID25663387}}.

==Development Time Course==

Melanocytes originate from neural crest cells, where they migrate to and localise in many different parts of the embryo during the first trimester of embryogenesis (in particular between weeks 4 to 18). Skin melanocytes follow hair follicles closely and localise around them, but little is known about melanocytes in volar skin (skin of the palms and soles), but it is suggested that they localise around eccrine sweat glands. {{#pmid:25818865|PMID25818865}}

Week 4= Visible neural plate where neural crest cells derive from.

Weeks 6-8= Melanoblast (pre-cursor cell of melanocytes) migration along dorsolateral trunk. Melanoblast proliferation also takes place along pathway, as the cells reach their areas of localisation, such as the eyes and the meninges. Melanoblasts have to migrate over incredibly long distances within the embryo, while at the same time proliferating and maintaining their chances of survival, so their development is a very dynamic process.

Weeks 9-12= Beginning of melanoblast migration to developing hair buds.

Weeks 12-13= A majority of melanoblasts are located in the epidermis and hair follicles. All melanoblasts differentiate into melanocytes.

Week 18= Hair breaks through skin surface containing melanocytes. {{#pmid:24278043|PMID24278043}}

==Molecular Mechanisms/ Factors/ Genes==

** unedited **
melanocytes in the skin-

transcription factors*
microphthalmia-associated transcription factor (MITF)

intrinsic factors:
- Hmx1
- Krox20

extrinsic factors modulating Hmx1 and Krox20:
- Neuregulin-1
- IGF
- PDGF

derivation pathways:
- differentiate from ncc via dorsolateral path
- from schwann cell precursors via ventral pathway

{{#pmid:24789876|PMID24789876}}.

==Animal Models==

===Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity During Melanoma Initation===

[[File:Zebrafish_Melanoma.jpeg|400px|thumb|center|Figure 7. Neural crest reporter expression in melanoma.]]

===Genetically Engineered Mice (GEM) Models For Melanocyte Development===
The development of melanocytes in mice and humans are very similar, except they take longer to form in humans, so mice can be used to study melanocytes as they would occur in the human body. SCF (melanocyte growth factor) is essential for the maintenance and survival of melanocytes throughout life. The receptor for SCF is c-''kit'', and if it mutates, it can lead to sterility, anaemia and pigmentation disorders. If the receptor is completely lost, it results in loss of melanocytes, primordial germ cells and haematopoietic stem cells completely. In embryonic development however, ETRB (endothelin receptor) is more important to melanocyte developed compared to c-''kit'', as it regulates the number of precursor melanoblasts that will differentiate into melanocytes.
{{#pmid:10985664|PMID10985664}}

[[File:GEM.jpeg|400px|thumb|center|Figure 8. Overall scheme for the generation of genetically engineered mice.]]

===Genetically Engineered Mice (GEM) Models For UV-induced Melanoma===
UV-induced melanoma is explored in GEM as the skin of a mouse is similar to the skin of a human except that mice are covered in hair that undergo frequent cycles for follicular development, which in turn causes mature melanocytes to be shed. There is also a distinct difference in the levels of eumelanin and pheomalanin between mice and humans. These mice models allowed scientists to study the part UVR plays in melanomagenesis, in particular those that over-expresses HGF (hepatocyte growth factor). {{#pmid:28092363|PMID28092363}}

==Current Research==

===Generation of Melanocytes from Induced Pluripotent Stem Cells (iPSCs)===
Melanocytes can be derived from autologous iPSCs, meaning the cells come from the one person. In this case the likelihood of the melanocytes being rejected by the immune system of the person they are being implanted in, is incredibly low. A benefit of autologous iPSCs from a patient with a pigmented disorder (such as albinism), is that the pathogenesis can be studied in order to find a suitable treatment for the disease, and possibly a cure. {{#pmid:23483397|PMID23483397}}

===Altered Chromosome Expression of Uveal Melanoma in the Setting of Melanocytosis===
Uveal melanoma seems to effect chromosomes 3p, 3q, 1p, 8p and 8q in particular as they show the most significant areas of DNA loss or amplification. However, the most important DNA alteration is monosomy on chromosome 3. In melanocytosis tissue, there is normalcy on chromosome 1, 3, 6 and 8, but there is exhibited disomy on chromosome 3. Ocular melanocytosis is predicted to impart a 1/400 lifetime risk of uveal melanoma in Caucasian individuals (which is 400x higher than the general population). It has been found that alterations in chromosome 3 does not always lead to the development of uveal melanoma, but it does take place sometime during the tumour development. {{#pmid:18547285|PMID18547285}}

==Abnormalities==
===Skin===
Abnormalities associated with melanocytes are often caused by disruptions to or loss of function of the pigmentation and its related factors. These pigmentary disorders are classified as hyperpigmentation disorder, hypopigmentation disorder, mixed hyperpigmentation disorder and mixed hypopigmentation disorder which are further subclassified into acquired and congenital {{#pmid:24789876|PMID24789876}}.

Hyperpigmentation disorders refer to an array of usually benign skin conditions characterised by the darkening in colour of patches of skin. The darkening in colour is caused by the deposition of an excess of melanin in the skin, thus ‘hyper’ pigmentation </ref> Aocd.org. Hyperpigmentation - American Osteopathic College of Dermatology (AOCD). [online] Available at: https://www.aocd.org/page/Hyperpigmentation.<ref>.

====LEOPARD Syndrome====

LEOPARD syndrome is a congenital hyperpigmentation disorder that causes abnormalities to the appearance and functioning of the skin, heart, genitalia and inner ears. </ref>Genetic and Rare Diseases Information Center. (2016). LEOPARD syndrome. [online] Available at: https://rarediseases.info.nih.gov/diseases/1100/leopard-syndrome<ref>.

====LEOPARD Syndrome====
LEOPARD syndrome is a congenital hyperpigmentation disorder that causes abnormalities to the appearance and functioning of the skin, heart, genitalia and inner ears. The name LEOPARD is an acronym which describes the characteristics of the condition;

L for Lentigines. These are pigmented macules (spots) on the skin.
E for Electrocardiographic conduction defects. Aberration in the electrical activity of the heart due to factors including arrhythmia, intraventricular conduction delay etc leading to cardiac abnormalities.
O for Ocular hypertelorism. An increased distance between the orbits within which they eyes lie resulting in widely spaced eyes.
P for Pulmonary stenosis. Abnormalities of blood circulation caused by an obstruction to the pathway of blood outflow from the right ventricle to the heart.
A for Abnormal genitalia.
R for Retardation of growth. Slowed growth leading to short stature.
D for Deafness. Sensorineural deafness (discussed below)

LEOPARD syndrome is autosomal dominant and can be inheritable. It can be caused by mutations to 3 different genes; protein tyrosine phosphatase, non-receptor type 11
(PTPN11), Raf-1 proto-oncogene (RAF1) or B-Raf proto-oncogene (BRAF). </ref>Genetic and Rare Diseases Information Center. (2016). LEOPARD syndrome. [online] Available at: https://rarediseases.info.nih.gov/diseases/1100/leopard-syndrome<ref>

The lentigines in LEOPARD syndrome are caused by the development of additional matured melanosomes in the melanocytes and keratinocytes. An experiment conducted by the Department of Dermatology at Gunma University Graduate school of Medicine in 2015 used in vitro assays to study the melanocytes of patients with LEOPARD syndrome. The in vitro assay of a patient with LEOPARD syndrome caused by a mutation in the PTPN11 gene showed that melanin synthesis in the patient’s melanoma cells were higher than those of unaffected individuals due to the melanoma cells’ expression of SHP-2. SHP-2 is the protein tyrosine phosphatase encoded by the PTPN11 gene. This discovery suggested that the mutations to SHP-2 when associated with LEOPARD syndrome cause an increase in melanin synthesis by the melanocytes, thus resulting in the large pigmented spots{{#pmid:25917897|PMID25917897}}.

===Ears===

====Waardenburg Syndrome====

There are varying forms of Waardenburg Syndrome, but they all result in deafness due to loss of melanocytes in the inner ears. As explained in the above section "Tissue Organ Structure and Function", melanocytes are necessary for sound transduction. The mutations that cause Waardenburg Syndrome, result in a lack of Melanogenesis Associated Transcription Factor (MITF) expression. MITF is a protein which works along side the transcription factor LEF-1 to regulate melanocyte gene expression {{#pmid:12032083|PMID12032083}}. These mutations may be in Sox10 and Pax3 genes, as these both regulate the expression of the MITF protein {{#pmid:10973953|PMID10973953}}{{#pmid:10982026|PMID10982026}}. Hence, Waardenburg Syndrome can have varying genetic causes, but with the same outcome.

====Sensorineural hearing loss (SNHL)====

===Eyes===

====Uveal Melanoma====
Melanoma that occurs in the eye is known as uveal melanoma. This is an uncommon form of cancer that only accounts for about 3% of all melanomas. The risk factors of this cancer are light skin colour, red or blonde hair and blue or light irises. {{#pmid:24508696|PMID24508696}}. About 95% of uveal melanomas occur in the posterior eye (the ciliary body and choroid). Even though this is a rare from of cancer, it still contributes to a large percent of deaths and has a high chance of leading to distant metastases despite successful initial therapies in the local tumour or tumours of the eye. {{#pmid:21305041|PMID21305041}}

===Heart===

===Central Nervous System===

==Glossary==

Autologous- cells or tissues obtained from the same individual

Melanoblasts- melanocyte pre-cursor cells

Melanocytosis- the presence of an excessive number of melanocytes

Melanoma- a tumour of melanin-forming cells

Melanogenesis - the production of melanin

Nevus- chronic lesion of skin or mucosa

Volar Skin- skin of the palms of the hands and the soled of the feet (thick skin)

==References==

2018 Group Project 3

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{{Editing Links}}

==Peer Assessment assignment:==

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]])

'''Group 1, Adrenal Medulla:'''
The History section is very detailed - more weight on the history of neural crest discovery related to the adrenal medulla specifically would be appreciated, as this is your topic, but I do think that it is good that you have maintained a focus on neural crest.

I think your section on genes and transcription factors is well described - I like that you have given a mouse model example. I presume the links to the sites will be added as proper references later. I also think the image of the cascade of catecholamine synthesis is helpful for those interested in the pathway, though its location is currently too far away from this section on the page. However, this is a minor issue and something that might be tidied up nearer the end of the assignment.

You currently don’t have any abnormalities/abnormal development information. It would be nice to see some example here such as Congenital Adrenal Hyperplasia.

In “current research” you have copied and pasted the introduction from the article cited. This definitely needs to be put into your own words, and maybe simplified as currently it is quite difficult to understand.

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]]) 11:19, 14 August 2018 (AEST)z5229132

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]])

'''Group 4, Cardiac:'''

You need to make both your “Introduction” and Development of the Cardiovascular System” headings proper headings using the “==“ signs either side. This development section otherwise is very well laid out and comprehensible. I like your use of video and the way you have done a week-by-week breakdown.

The rest of your website is very well written and descriptive - I’m especially impressed by the detail in the development sections, and how you manage to convey the information clearly. It might be helpful to see a few images or figures showing the breakdown of this development to break up the text a little, but your subheadings are very helpful.

The CHARGE Syndrome section has a couple of issues with phrasing in the paragraph below the link, which you might wish to address.

The end of your website appears unfinished, for example in “human congenital heart diseases associated with Neural crest cells”; “research” and “animal models”, more detail and editing is required. You also have one referencing error which needs addressing. Overall, I am very impressed by your page.

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]])
'''Group 5, Dorsal Root Ganglion:'''

The introduction is currently very brief, but this is probably one of the final parts of the webpage that you will address.

It would be good if you had a little bit of information on the history of the Dorsal Root Ganglion/neural crest discovery.

I find the second paragraph of Embryonic Origins a little confusing - it is unclear whether you are saying that the DRG cells are already differentiated before migration, or whether this happens after. This process is better explained/repeated a little in the next section on development process. Maybe the Embryonic origins section should be simplified to just describing the location of the original neural crest cells, if migration is mentioned later anyway.

In “Tissue Structure” there are a few errors in writing that require addressing. I like your drawn diagram - it complements the paragraph’s description well. The placement of the image is slightly off, but this can be adjusted in your final edits.

Your Molecular mechanisms/factors/genes section is very thorough and clearly described. A figure showing the flow of events in the signalling pathway might be helpful to go along with this.

You need to reference your abnormality section, and edit its format a little, as currently the image seems out of place.

The animal models section is really interesting and well written, but it needs referencing at the start.

I’m impressed with the “Current Research” section - it is well written and the image is interesting and complements the paragraph.

You have used a broad range of references for this site, which shows you have done some extensive research on your topic.

==Lab 3==

==Lab 2==
[[Help:Image Tutorial]]

[[File:Neuropore cell shape changes.png|400px]]

Neuropore cell shape changes{{#pmid:30064364|PMID30064364}}

<references/>

==Reference==

Physiology and Pathophysiology of Inner Ear Melanin{{#pmid:3070525|PMID3070525}}

Talk:2018 Group Project 5

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[[User:Z5229399|Z5229399]] ([[User talk:Z5229399|talk]]) 11:33, 14 August 2018 (AEST)
[[User:Z5229597|Z5229597]] ([[User talk:Z5229597|talk]]) 11:34, 14 August 2018 (AEST)
[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 11:35, 14 August 2018 (AEST)
[[User:Z5229549|Z5229549]] ([[User talk:Z5229549|talk]]) 11:36, 14 August 2018 (AEST)
[[user:Z5229438|Z5229438]] ([[User talk:Z5229438|talk]]) 11:36, 21 August 2018 (AEST)

==Peer Reviews (Lab 10)==
[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 18:02, 4 October 2018 (AEST)
The flow of the introduction seems rather abrupt between the two sentences, but I assume that the introduction is not completed yet.

In embryonic origins, Dorsal root ganglion was mentioned as DRG in the 2nd paragraph. You might want to introduce this abbreviation beside the term at the first paragraph: Dorsal Root Ganglion (DRG) so that the reader can easily understand what you are referring to.

Some typos can be seen through out the wiki page like migratio and the format of the referencing is not consistent "lateral to the neural tube. [3]." and "lowed quickly by the precursors that shape the development of TrkA.[8]." as compared to other parts of the wiki: "during later stages following migration. [6]"

Content wise, the project seems to be doing fine with tons of references and content (with exception of the empty sections like History).

The videos were not uploaded on the page properly (under the current research section), so you might want to fix that.

[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:14, 3 October 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:14, 3 October 2018 (AEST)
There has been an extensive use of references which is great especially since this topic seems to be really complex. Maybe a few more images for the beginning part of the article will make it look more user-friendly. Definitely have a look over for any grammar/spelling issues.

** Embryonic origins has been well-written. Proof-read for typing errors. Neural crest migration section shows good research and use of terminology. Neuronal and glial development has nice concise information though it might be wise to add some more content. Also if the heading will be Glial dev, then neuron dev should be changed to Neuronal dev- for consistency. Adult function of ? However, this section is well-written! Concise and relevant- great work guys! Tissue Structure is starting to look good however needs more content. Really good student drawn image!! Though it might be good to be the image higher up on the page.

Molecular mechanisms/factors/genes has overall been well written. Perhaps a brief statement about what transcription factors are?
Interesting image in abnormalities. I would personally appreciate an explanation of what I am seeing in the image. More discussion of a wider variety of abnormalities might be beneficial.
Excellent coverage of animals models so far!! May be one more? Also, great use of images!
Current research seems to be coming along well! Some formatting edits so that the video appears on the page would be good!

Overall, great work guys! Keep it up and move along with the project consistently! :) **

[[User:Z5113627|Z5113627]]

History - empty, try and look for history of spinal nerve embryological discoveries as a potential starting point!

Embryonic Origins - good information, nice to read, but try and clean up the syntax just a little bit.

Developmental Process - Very clean and finished section with a thorough understanding of chemical mediators, overarching anatomy and embryological concepts.

Axonal Targeting - Try cleaning up the second sentence on Receptor Tyrosine Kinases, very good section otherwise.

Neuron Development - Good description of chemical mediators and their involvement in embryological processes

Glial Development - Also very good, as above. Consider adding a diagram or table, to simplify the knowledge into something your classmates can easily comprehend.

Adult Function - Could be mixed in with Tissue structure as one topic, otherwise both are good and set the stage of adult role & neurophysiology well.

Molecular Mechanisms - Fantastic all-round, not very much to fault, just try and preen up sentences here and there and proof-read, consider adding a little more information in a few sections, but only what would be necessary for the specific embryology.

Abnormalities, Animal Models and Current Research - All very well done, try simplifying some of the sentences occasionally.

References - Very good as well.

[[User:Z5160977|Z5160977]] ([[User talk:Z5160977|talk]]) 12:19, 5 October 2018 (AEST)

It would be good if there was a more fleshed out introduction, that outlined the purpose and scope of the project. The referencing is very comprehensive and shows that a lot of research has been put in. The information is presented will and is very in depth. In the Molecular Mechanisms section, I would suggest an introduction sentence or two, to tie the section together and help it to flow, overall it looks on track, but I would recommend having a think about the flow of the project and the layout of the information in terms of subheadings, an introduction would help to make that flow clear.

[[User:Z5229281|Z5229281]]

The references and images are great. I would like more of a description on the image in the neural crest migration to the DRG section as it seems brief and I am a little lost, maybe add information on what the colors are specifically so I know what I am looking at. That section is extremely well written with loads of information which is great. In the section glial development, the descriptions of the proteins and what they do would help me understand such as proteins SOX10 and P2x3 in the section there is information on the proteins but not specifically where they are form and what functions they have. The last thing is just fix up the glossary and history section and the project is complete and nicely done dorsal root ganglia group.

[[User:Z5112688|Z5112688]] ([[User talk:Z5112688|talk]])
Overall the project is structured decently but I think the flow of the page could be improved. A clear introduction would help greatly as well as grammatical errors being fixed.History has been left unanswered. The Developmental process section is clear and concise. One improvement I can think of is to add some more images or other forms of media to make it more interesting rather then just text. For signalling pathway the information seems too brief, more explanation is needed. The image in abnormalities should have some text or something to explain its significance otherwise its hard for the readers to understand the purpose of the image. The animal models and current research section is really good. The information is interesting and relevant images have been used to further improve the educative purpose of the page. References is quite detailed showing a good amount of research being done on project.

[[User:Z5229549|Z5229549]] ([[User talk:Z5229549|talk]]) 18:17, 6 October 2018 (AEST)
Wiki page seems pretty much fleshed out with a decent number of diagrams. Some of the sections under development could be more concise. Introduction appears to be lacking as the history. The flow of the entire page however, needs touching up as it feels very choppy to read. Also, less technical jargon could be used to provide a more concise descript of some of the development sections.

Overall, a more or less complete page, disregarding the introduction and history. Well referenced with adequate visual aid.

Group 5, Dorsal Root Ganglion:

The introduction is currently very brief, but this is probably one of the final parts of the webpage that you will address.

It would be good if you had a little bit of information on the history of the Dorsal Root Ganglion/neural crest discovery.

I find the second paragraph of Embryonic Origins a little confusing - it is unclear whether you are saying that the DRG cells are already differentiated before migration, or whether this happens after. This process is better explained/repeated a little in the next section on development process. Maybe the Embryonic origins section should be simplified to just describing the location of the original neural crest cells, if migration is mentioned later anyway.

In “Tissue Structure” there are a few errors in writing that require addressing. I like your drawn diagram - it complements the paragraph’s description well. The placement of the image is slightly off, but this can be adjusted in your final edits.

Your Molecular mechanisms/factors/genes section is very thorough and clearly described. A figure showing the flow of events in the signalling pathway might be helpful to go along with this.

You need to reference your abnormality section, and edit its format a little, as currently the image seems out of place.

The animal models section is really interesting and well written, but it needs referencing at the start.

I’m impressed with the “Current Research” section - it is well written and the image is interesting and complements the paragraph.

You have used a broad range of references for this site, which shows you have done some extensive research on your topic.

==Introduction==
*A good article for the overview of trunk neural crest cells

{{#pmid:28287247}}

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 12:25, 24 August 2018 (AEST)

*Image about entire overview of neural crest migration

==History==

*find a image for the overview of DRG development
*if cannot find, use animal species to draw out the timeline
*work on chicken to identify origins of different components of DRG, neural crest
*timeline of discovery of DRG (use date of publication to put the timeline, around 1970s, original discovery is around 1930s)
*if cannot find about DRG, find about trunk neural crest

==Embryonic Origins==
*which particular part of the neural crest contribute to the DRG
*do they differentiate during migration or do they differentiate only when reaching the location
*which particular mechanism influence the differentiation process into DRG

==Developmental Process==
*extension of DRG to different end points (epithelium, joints, muscle fibres)
*good to include a timeline (schwann cells -> differentiation and myelination)
*understanding schwann cell differentiation and myelination
*neuronal cell death (apoptosis if they do not reach the cell type)

==Adult Function==
*Differentiation process
*When they start to function
==Tissue / Organ structure==
==Molecular Mechanisms / Factors / Genes==
*Tim

"Blocking of CXCR4 by morpholino or shRNA in premigratory chick trunk neural crest cells leads to significantly fewer cells that reach the dorsal aorta and instead populate the dorsal root ganglia"

{{#pmid:20881125}}

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 12:18, 24 August 2018 (AEST)

*summary of signalling pathway and their interactions with each other
*identifying if molecular factors are growth or transcription factors

==Abnormalities / Abnormal development==
Dorsal Root Ganglionopathy is responsible for sensory impairment in CANVAS

“[[File:Dorsal Root Ganglion disorder.jpg]]”

"Sensory ganglionitis, variably called ganglionopathy, is a disease of sensory neurons in dorsal root ganglia. Major forms of these diseases are associated with neoplasm, Sjögren syndrome, and paraproteinemia or polyclonal gammopathy with or without known autoantibodies. Most cases follow subacute courses, but there are forms that develop chronically and acutely as well. Clinical signs seen include sensory ataxia exhibited by gait unsteadiness, a positive Romberg sign, reduced deep tendon reflexes, poor coordination, and pseudo-athetoid movements in the hands. Axonal degeneration warrants the treatment as early as possible. Early cases of immunologic origin that are immune-mediated may respond to plasmapheresis and immunosuppression. Differential diagnoses include environmental and industrial intoxication and adverse effects of antineoplastic and antibiotic drugs. The term “sensory neuronopathy” or “ganglionitis” refers to disorders of small neurons, larger neurons, and/or neurons of both sizes in the sensory ganglia."

==Animal Models==
"In zebrafish, trunk NCCs start migrating along a medial pathway in-between the somites and the NT. These NCCs align to and are affected by slow muscle cells in the middle part of the somite"

{{#pmid:16162652}}

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 12:16, 24 August 2018 (AEST)

"Hedgehog (Hh) signal transduction is directly required in zebrafish DRG precursors for proper development of DRG neurons. Zebrafish mutations in the Hh signaling pathway result in the absence of DRG neurons and the loss of expression of neurogenin1 (ngn1), a gene required for determination of DRG precursors. Cell transplantation experiments demonstrate that Hh acts directly on DRG neuron precursors. Blocking Hh pathway activation at later stages of embryogenesis with the steroidal alkaloid, cyclopamine, further reveals that the requirement for a Hh signal response in DRG precursors correlates with the onset of ngn1 expression. These results suggest that Hh signaling may normally promote DRG development by regulating expression of ngn1 in DRG precursors."

Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons. Josette M. Ungos, Rolf O. Karlstrom, David W. Raible. Development 2003 130: 5351-5362; doi: 10.1242/dev.00722

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 00:25, 28 August 2018 (AEST)

[[File:Neural crest cell migration in erbb3b mutants.jpg]]

"Dorsal root ganglia (DRGs) arise from trunk neural crest cells that emerge from the dorsal neuroepithelium and coalesce into segmental streams that migrate ventrally along the developing somites. Proper formation of DRGs involves not only normal trunk neural crest migration, but also the ability of DRG progenitors to pause at a particular target location where they can receive DRG-promoting signals. In mammalian embryos, a receptor tyrosine kinase proto-oncogene, ErbB3, is required for proper trunk neural crest migration. Here, we show that in zebrafish mutants lacking ErbB3 function, neural crest cells do not pause at the location where DRGs normally form and DRG neurons are not generated. We also show that these mutants lack trunk neural crest-derived sympathetic neurons, but that cranial neural crest-derived enteric neurons appear normal. We isolated three genes encoding neuregulins, ErbB3 ligands, and show that two neuregulins function together in zebrafish trunk neural crest cell migration and in DRG formation. Together, our results suggest that ErbB3 signaling is required for normal migration of trunk, but not cranial, neural crest cells."

{{#pmid:18599505}}

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 00:37, 28 August 2018 (AEST)

"cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk."

{{#pmid:26256768}}

[[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 00:45, 28 August 2018 (AEST)

==Current research (Labs)==
--[[User:Z5229438|Z5229438]] ([[User talk:Z5229438|talk]]) 19:27, 27 August 2018 (AEST)
==Glossary==
*Brief, clear and concise
==Reference==

*HAVE A LIST OF ACRONYMS TO CONDENSE THE INFORMATION

User:Z5229132

2018-10-06T11:19:51Z

Z5229132: /* Peer Assessment assignment: */

User:Z5229132

2018-10-06T11:14:51Z

Z5229132: /* Peer Assessment assignment: */

Talk:2018 Group Project 4

2018-10-06T11:13:49Z

Z5229132: /* Peer Reviews (Lab 10) */

{{2018ANAT2341ProjectHeader}}
= Neural Crest and Cardiovascular Development =
{{2018ANAT2341ProjectDiscussion}}



==Peer Reviews (Lab 10)==
[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:10, 3 October 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:10, 3 October 2018 (AEST)
This project is coming along very well. Perhaps consider using a few more references as your list seems short. Also, I did like the use of a video but ideally it should be very short. I don't feel that many people will actually watch a 9 minute video. Perhaps a stop motion clip or a flow chart summary could replace this to make it easy to understand? Overall this is great work and seems to be a rather complex topic. Keep it up group 4.

[[User:Z5164785|Z5164785]] Some editing required for the formatting (introduction, development of the cardiovascular system etc)
Good use of the video- excellent aid for later understanding of what you guys discuss!

Great research exhibited in the cardiac neural crest cells section; an image to go beside it would be great. References need to be formatted correctly so that they are’t displayed in the written information.

I like how early development has been broken down. However, how come they’re numbered here but not in later development? Clear and concise information presented in induction. In the neural crest to circumpharangeal ridge section, perhaps bold/underline the signalling factors so it’s clear. The formation of pharyngeal arches … section also has good information! An image for this section especially would be beneficial.

As a whole, the later development section is also good. Mostly clear and concise information.  Some proof-reading would be good.

Some more information about the signaling molecules would be good- perhaps tie to back to what was mentioned in the circumpharangeal section?

The time course is also good! I like the selection of heart diseases and how they’ve been discussed. Perhaps some additional information about symptoms, epidemiology etc would be good but that’s just a suggestion.

Overall, great work guys! Keep it up and move along with the project consistently! Perhaps include some student-drawn images. I like the planning- if you keep at it you’ll have an awesome project!

[[User:Z5229189|Z5229189]] ([[User talk:Z5229189|talk]]) 12:28, 14 August 2018 (AEST)

Points to take note:
- Need to describe in content how neural crest links to development of heart, rather than just talking about development of heart
- Acronyms used to be listed at end of page
- Correct Referencing

[[User:Z5113627|Z5113627]]

Introduction - Short but does nicely explain some of the important aspects of cardiogenesis, the sentences could be ordered more cleanly and could allude to more than just animal models and their connection to neural crest and DiGeorge Syndrome in humans. History of knowledge of cardiogenesis maybe?

Development of the Cardiovascular System - Could possibly be retitled? (There is no mention of peripheral vasculature that is a part of the cardiovascular system, you have simply referred to cardiogenesis: the formation of the heart). The developmental timecourse is good at explaining the important events in cardiogenesis and what weeks they correspond to. The embedded video is also good, but is quite long at 9 minutes.

Cardiac Neural Crest Cells - This is a good introduction to the specific neural crest population that contribute to cardiogenesis. However, there are a few issues with sentence formatting, grammar and referencing that could be cleaned up. The mention of neural crest's pluropotentiality is perfect in understanding how the different tissue types of the valvular structures arise, so that is definitely a strong point of the section.

Early Development - Very good, key chemical mediators are mentioned, could more be explained about what they are and how they relate to neural crest specifically? An explanation on the circumpharyngeal ridge would also be welcomed.

Later Development - Very nice partitioning diagram, Valvulogenesis section could be longer, it is very important. The same can be said for Atrial and Ventricular Separation.

Signalling Molecules - Good overview, more links to literature would be appreciated than just Meis-2, more could be added if necessary to discussion.

Developmental Time Course appears incomplete, this needs to be more specific.

Abnormalities - Seem quite well discussed, formatting needs some work as well as general cleaning with references, diagrams of a histology section or relevant macroscopic specimen would be welcome here to understand the pathology and how it relates to the embryology.

Research - Same as above, but there seems to be less information as well: there needs to be more content, directed referencing, images if necessary, and specific examples of mutant, knock-out or other genetically-engineered models to observe these embryological findings. There is good mention of the different animal models that are used to observe cardiogenesis (mouse, fish and chicken) but otherwise, it needs some work.

Glossary and References - Very few current references at the bottom, I assume this is because the bulk of them have not been formatted correctly, most appear to be from research literature and medical science journals, no current glossary might be an issue if there are many acronyms.

[[User:Z5160977|Z5160977]] ([[User talk:Z5160977|talk]]) 12:06, 5 October 2018 (AEST)
An introduction would be helpful to outline the project and bring in an understanding of development and neural crest contribution. The overview of the heart is very clear and detailed. Referencing needs a bit of work to ensure that the information is valid. There is a lot of in depth information which gives a detailed understanding of neural crest contribution to cardiac development. I would suggest reconsidering the structure, for example putting the developmental timeline earlier in the project.

[[User:Z5112688|Z5112688]] ([[User talk:Z5112688|talk]])
Overall the page is logically structured, great use of images and other forms of media to get point across. Introduction is too brief, should give an overview of everything that is to be covered in the page. The use of a timeline is a really good choice and easy to understand. The cardiac neural crest cells section has a clear description and dot points make it easy to read and understand. The early parts of the page look very good. Have something that explains what the purpose of the heart embryology video. There are areas in the latter half of project that still need to be covered, however the information that is present is clear and easily understandable. I do believe that the information should link the neural crest development and cardiovascular development should be present. Right now the cardiac development has been covered in enough detail. The references should be properly formatted to make the project look better structured.

[[User:Z5229549|Z5229549]] ([[User talk:Z5229549|talk]]) 17:52, 6 October 2018 (AEST)
A quick glance of the entire page revealed a relative lack of visual aids, discounting the embed video and a diagram showing a step-by-step development of the heart in a fetus. Use of tables and point form sentences in each section do help break up chunks of words, allowing a more bearable read. It is good if the format, heading and structure-wise could be standardised throughout in a show of better professionalism.

The introduction is short but concise. It would be viable to include some context history of the study's beginning and development. More explanation in early development without an overuse of technical jargon is advisable. Noticed that Models and Research is not yet fully written. The inclusion of recent discoveries of cardiac diseases would make it more interesting.

Overall, the content seem to be more or less there, withholding certain sections where it is too brief. Format and structure needs a little work, and inclusion of more visual aids is viable.

Group 4 Review:

You need to make both your “Introduction” and Development of the Cardiovascular System” headings proper headings using the “==“ signs either side. This development section otherwise is very well laid out and comprehensible. I like your use of video and the way you have done a week-by-week breakdown.

The rest of your website is very well written and descriptive - I’m especially impressed by the detail in the development sections, and how you manage to convey the information clearly. It might be helpful to see a few images or figures showing the breakdown of this development to break up the text a little, but your subheadings are very helpful.

The CHARGE Syndrome section has a couple of issues with phrasing in the paragraph below the link, which you might wish to address.

The end of your website appears unfinished, for example in “human congenital heart diseases associated with Neural crest cells”; “research” and “animal models”, more detail and editing is required. You also have one referencing error which needs addressing. Overall, I am very impressed by your page.

=Neural Crest and Cardiac Development=

===Introduction/histology/anatomy/physiology===

===History of cardiac neural crest cells===

https://www.ncbi.nlm.nih.gov/pubmed/17429214

https://www.ncbi.nlm.nih.gov/pubmed/29158447

===Structure of the Heart===
The heart is a muscular organ which plays a critical role in the circulatory system by mechinically pumping blood to various organs around the body for the exchange of nutrients and gases. It is located..... The heart has four different chambers which are compartmentalized by semilunar and atrioventricular valves into the left and right atria and ventricles
[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 11:43, 4 September 2018 (AEST)

"During early development, neural folds are formed along the anteroposterior-axis in the ectoderm. Upon fusion, the folds give rise to the neural tube. During the process of neural tube formation, cells detach at the border of the neural and epidermal ectoderm, i.e. at the dorsal aspect of the forming neural tube. These cells are referred to as neural crest cells. Neural crest cells migrate along defined pathways throughout the body. Upon arrival at their destination, they differentiate into various cell types, among which melanocytes, peripheral neurons and their supporting cells, and skeletal elements. The neural crest cells are formed along the entire cranio-caudal axis of the body and can be divided into two major populations the cranial and truncal neural crest cells. The cranial neural crest extends from the diencephalon up to somite pair 5, and the truncal neural crest from somite pair 6 to the caudal end of the neural tube. The truncal neural crest is involved in sympathetic innervation of the heart, whereas the cranial neural crest is associated with parasympathetic innervation of the heart."

{{#pmid:10946058}}

[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 11:51, 21 August 2018 (AEST) Sounds good for a brief introduction of the neural crest roles to the heart development

"The subpopulation of neural crest cells responsible for aorticopulmonary septation has been termed the cardiac neural crest. CNCCs are required for the normal development of the thymus, thyroid, parathyroids, cardiac conduction system, semilunar valves, parasympathetic innervation of the heart, and outflow septum, as well as proper remodeling of the pharyngeal arch arteries and alignment of the outflow with the ventricles. "

{{#pmid:25227322}}

[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 07:40, 23 August 2018 (AEST)

This page will give a brief understanding of the cardiac anatomy and how the organ develops. To give the reader a basis of how the neural crest forms the heart n and all of its valves and what happens when mechanisms (abnormal migration patterns) of the neural crest cause malfunctions and generate deformities in the growing embryo.

===Embryonic origins/embyronic contributions===
https://onlinelibrary.wiley.com/doi/full/10.1002/bdrc.21081
This article is great for the origins/process of the neural create, basic information in terms readable by most and will be a basis fro understanding the neural crest.

The neural crest is the name given to the strip of cells at the junction between neural and epidermal ectoderm in neurula‐stage vertebrate embryos, which is later brought to the dorsal neural tube as the neural folds elevate. The neural crest is a heterogeneous and multipotent progenitor cell population whose cells undergo EMT then extensively and accurately migrate throughout the embryo. Neural crest cells contribute to nearly every organ system in the body, with derivatives of neuronal, glial, neuroendocrine, pigment, and also mesodermal lineages. This breadth of developmental capacity has led to the neural crest being termed the fourth germ layer.

https://onlinelibrary.wiley.com/doi/full/10.1002/bdrc.21081#citedby-section

numerous authors collaborated on the information above.

===Early development===
"Cardiac neural crest cells originate from the neural tube extending from the axial level of the mid otic placode to the third somite in chick. The cells then migrate from the neural tube into the caudal pharyngeal arches (3, 4 and 6). Some neural crest cells remain in the pharynx to support aortic arch artery development, while a subpopulation continues on to migrate into the outflow tract of the heart"

{{#pmid:22595346}}

[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 09:22, 28 August 2018 (AEST)

[[File:Progressive development of the Embryonic Heart.jpeg|750px]]
[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 11:13, 24 August 2018 (AEST)

[[File:Cardiacdevelopment1.jpg]]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375817/
[[User:Z5229177|Z5229177]] ([[User talk:Z5229177|talk]]) 09:07, 28 August 2018 (AEST)

===Later development===
===Developmental time course/carnegie stages/overview===
===Cell signalling involved/molecular mechanisms/factors/genes===
https://discovery.lifemapsc.com/library/images/neural-crest-development
photo I want to use for the project

[[File:Migrating Neural Crest cells.png]]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113226/

Article talking about hormones regulating the migration of neural crest cells to different destinations of the body.

===Disorders/abnormalities===
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389200/ Article explains congenital defects of the heart from the neural crest and how the defects happen at the molecular level

"Cardiac neural crest ablation experiments demonstrated that upon removal of the pre-migratory cardiac neural crest cardiovascular abnormalities are induced. The pre-migratory neural crest is ablated by removal of the dorsal aspects of the neural folds using vibrating needles, tungsten needles, or laser. Entire removal of the cardiac neural crest showed in almost all cases a persistent truncus arteriosus (PTA). However, the chicken neural crest ablation phenotype also includes abnormal patterning of the great arteries that are derived from the aortic arches, absence or hypoplastic thymus, thyroid and parathyroids. As expected, removal of only the cardiac neural crest does not effect the innervation of the heart and does not lead to craniofacial abnormalities. Interestingly, partial ablation of the cardiac neural crest results in a milder cardiac phenotype, like double outlet right ventricle, dextraposed aorta, tetralogy of Fallot, and/or ventricle septum defect, whereas the other phenotypic alterations are hardly different from complete cardiac neural crest ablation [17,26–29]. Based on these ablation studies it was concluded that PTA only occurred when the numbers of neural crest cells were reduced below a critical level that is no longer compatible with proper formation of the aortico-pulmonary septum [5,30]. Thus, the ablation experiments are in agreement with the conclusion of Conway and coworkers [1] suggesting that the quantity rather than the quality of neural crest cells is important in OFT septation."

{{#pmid:10946058}}

[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 11:58, 21 August 2018 (AEST)

=== Brief overview of Heart Development===
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC408374/ Explains heart development, great for basic understanding and good for continuing research about the heart.

===Current research/main animal models/future questions===

==Reference==
PMID: 10359559
{{#pmid:10359559}}

<pubmed limit=5>Neural Crest Embryology</pubmed>

A novel role for cardiac neural crest in heart development

PMID: 10359559
{{#pmid:10359559}}

=Google doc=

Discussed between all group members on google docs.

Neural crest and cardiovascular development/cardiac neural crest
OUTFLOW TRACT
VALVE

Group project 2017 on heart development: https://embryology.med.unsw.edu.au/embryology/index.php/2017_Group_Project_3

The key points relating to the topic that your group allocated are clearly described.
The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
Content is correctly cited and referenced.
The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
Relates the topic and content of the Wiki entry to learning aims of embryology.
Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
Develops and edits the wiki entries in accordance with the above guidelines.

What should be on the page:
Table of contents
Introduction
History
Embryonic origins/embryonic contributions
Carnegie stages
Early development
Later development
Structure of the cardiovascular network
Developmental time course
Developmental/adult function
Tissue/organ structure / histology
Cell signalling involved/Molecular mechanisms/factors/genes
Anatomy of the cardiov
Functions of the cardiov
Abnormalities associated with the development of the cardiov
Models and Research (past/current/future)
Disorders: DiGeorge syndrome
Main animal model system
Current research (labs)
Future questions
Glossary (for all the acronyms)
Reference list

SO:
introduction/history/structure of the cardiovascular network/histology/anatomy/physiology
Embryonic origins/embyronic contributions
Early development
Later development
Developmental time course/carnegie stages/overview
Cell signalling involved/molecular mechanisms/factors/genes
Disorders/abnormalities:
Current research/main animal models/future questions

how to write a good project:
content
its brevity and balance between text and images: dont make it pages & pages on text ,it is a webpage!! balance the content. Keep your editing tight. Don’t make your whole project bulletpoints.
Like to see some drawings done by ourselves

Good articles on neural crest & cardiovascular development:

https://search.proquest.com/docview/222534802?pq-origsite=gscholar

https://www.ncbi.nlm.nih.gov/pubmed/25662261 (REVIEW article)

https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Neural_Crest_Development → Neural crest lecture

https://www.sciencedirect.com/science/article/pii/S0301468112000667?via%3Dihub (Review article by AnnaKeyte, Mary Redmond)
-> The neural crest in cardiac congenital anomalies/ a little on history

https://www.ncbi.nlm.nih.gov/books/NBK10065/ Article gives a good synopsis of nerual crest cardiac development.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC408374/ Article has a lot of information about heart development from the nerual crest, great article to start out with for beginning infromation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389200/
Congential defects of the heart during development and abnormalities, article with substantial information about what happens to the heart when the nerual crest is defected.

https://www.heartrhythmjournal.com/article/S1547-5271(06)02148-5/fulltext Great review article that has a lot of references to other scholarly papers we can use for a better understanding and more in depth information about cardiac valves.

https://www.ahajournals.org/doi/abs/10.1161/01.res.0000259041.37059.8c Essential protein needed for cardiac development.

https://www.ncbi.nlm.nih.gov/pubmed/25227568
This article gives a great description of the neural crest and the history of the neural crest and good information that is basic and informative. Will allow us to get the introduction of our webpage started and will be a branching point to move forward.

1: Introduction/history/structure of the cardiovascular network/histology/anatomy/physiology
→ Also explain what neural crest cells are?

History: (In a chick study of parasympathetic innervation of the heart, Margaret Kirby and colleagues ablated neural crest and serendi
pitously discovered that the embryos lacked aorticopulmonary septation (Kirby et al., 1983). The subregion of cranial neural crest ablated by Dr. Kirby has been called the “cardiac neural crest”, not because the cells of this region migrate solely to the heart, but for the importance of crest-derived ectomesenchyme in cardiovascular development.) -> Article by Anna Keyte

2: Embryonic origins/embryonic contributions

Neural crest at the level of the body have two general migration pathways, defined by the position of the somite:
medial pathway: between the neural tube and the somite
Lateral pathway: between the somite and the body wall (cardiac NCC)

Outflow tract
Valves

Cardiac neural crest cells (CNCCs) are a type of neural crest cells that migrate to the circumpharyngeal ridge (an arc-shape ridge above the pharyngeal arches) and then into the 3rd, 4th and 6th pharyngeal arches and the cardiac outflow tract. They extend from the otic placodes (the structure in developing embryos that will later form the ears) to the third somites (clusters of mesoderm that will become skeletal muscle, vertebrae and dermis). The cardiac neural crest cells have a number of functions including creation of the muscle and connective tissue walls of large arteries, parts of the cardiac septum, parts of the thyroid, parathyroid and thymus glands. They differentiate into melanocytes and neurons and the cartilage and connective tissue of the pharyngeal arches. They may also contribute to the creation of the carotid body, the organ which monitors oxygen in the lood and regulates breathing.

--- BEFORE THE CARDIAC NEURAL CREST CELL --

3: Early development

In higher vertebrates:
Cells in the cranial neural crest migrate in clusters or “streams” and later form cranial nerve ganglia at even-numbered rhombomeres proximally.
Specifically, the cranial crest migrates in three streams referred to as first or cranial, second or middle and third or caudal. The caudal stream comprises most of the cardiac crest. The majority of the crest emanate from the even numbered rhombomeres.

4: Later development

5: Developmental time course/carnegie stages/overview

6: Cell signalling involved/molecular mechanisms/factors/genes

Neural Crest Cells (NCCs) is essential in earlier stages of arterial valve development such as positioning the cushions and patterning valve leaflets (patterning)

7: Disorders/abnormalities

Abnormalities of arterial valves (Bicuspid aortic valve BAV)
DiGeorge syndrome

-Failure of outflow septation is a hallmark of cardiac neural crest ablation and is called persistent truncus arteriosus (PTA) (6–8). The common outflow vessel usually arises from the right ventricle and is always accompanied by abnormal patterning of the great arteries (9, 10).The most severe alteration in ventricular function is decreased ejection fraction. In addition to changes in ventricular function, abnormal morphology of the heart loop in early neural crest–ablated embryos has been reported (7, 13–16). All of these data indicate that cardiac neural crest ablation affects early heart development.

8: Current research/main animal models/future questions

Focus on overview of how the heart develops don't go too much in depth or else the project becomes a cardiac development page and that is not what the project is about. Go in depth to how the neural crest leads to abnormalities of the heart and what the neural crest does. Be brief about the heart development to give the reader a basic understanding about the heart then in depth discussion and development about the neural crest.\

[[User:Z5229281|Z5229281]] ([[User talk:Z5229281|talk]]) 12:47, 14 August 2018 (AEST)

[[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 12:48, 14 August 2018 (AEST)

[[User:Z5229177|Z5229177]] ([[User talk:Z5229177|talk]]) 12:49, 14 August 2018 (AEST)

[[User:Z5229189|Z5229189]] ([[User talk:Z5229189|talk]]) 12:51, 14 August 2018 (AEST)
[[User:Z5229281|Z5229281]] ([[User talk:Z5229281|talk]]) 12:05, 21 August 2018 (AEST)z5229281[[User:Z5229281|Z5229281]] ([[User talk:Z5229281|talk]]) 12:05, 21 August 2018 (AEST)

User:Z5229132

2018-10-06T10:48:42Z

Z5229132: /* Peer Assessment assignment: */

User:Z5229132

2018-10-06T10:47:52Z

Z5229132: /* Peer Assessment assignment: */

{{Editing Links}}

==Peer Assessment assignment:==

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]])

'''Group 1:'''
The History section is very detailed - more weight on the history of neural crest discovery related to the adrenal medulla specifically would be appreciated, as this is your topic, but I do think that it is good that you have maintained a focus on neural crest.

I think your section on genes and transcription factors is well described - I like that you have given a mouse model example. I presume the links to the sites will be added as proper references later. I also think the image of the cascade of catecholamine synthesis is helpful for those interested in the pathway, though its location is currently too far away from this section on the page. However, this is a minor issue and something that might be tidied up nearer the end of the assignment.

You currently don’t have any abnormalities/abnormal development information. It would be nice to see some example here such as Congenital Adrenal Hyperplasia.

In “current research” you have copied and pasted the introduction from the article cited. This definitely needs to be put into your own words, and maybe simplified as currently it is quite difficult to understand.

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]]) 11:19, 14 August 2018 (AEST)z5229132

==Lab 3==

==Lab 2==
[[Help:Image Tutorial]]

[[File:Neuropore cell shape changes.png|400px]]

Neuropore cell shape changes{{#pmid:30064364|PMID30064364}}

<references/>

==Reference==

Physiology and Pathophysiology of Inner Ear Melanin{{#pmid:3070525|PMID3070525}}

User:Z5229132

2018-10-06T10:47:20Z

Z5229132:

{{Editing Links}}

==Peer Assessment assignment:==

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]])
Group 1:
The History section is very detailed - more weight on the history of neural crest discovery related to the adrenal medulla specifically would be appreciated, as this is your topic, but I do think that it is good that you have maintained a focus on neural crest.

I think your section on genes and transcription factors is well described - I like that you have given a mouse model example. I presume the links to the sites will be added as proper references later. I also think the image of the cascade of catecholamine synthesis is helpful for those interested in the pathway, though its location is currently too far away from this section on the page. However, this is a minor issue and something that might be tidied up nearer the end of the assignment.

You currently don’t have any abnormalities/abnormal development information. It would be nice to see some example here such as Congenital Adrenal Hyperplasia.

In “current research” you have copied and pasted the introduction from the article cited. This definitely needs to be put into your own words, and maybe simplified as currently it is quite difficult to understand.

[[User:Z5229132|Z5229132]] ([[User talk:Z5229132|talk]]) 11:19, 14 August 2018 (AEST)z5229132

==Lab 3==

==Lab 2==
[[Help:Image Tutorial]]

[[File:Neuropore cell shape changes.png|400px]]

Neuropore cell shape changes{{#pmid:30064364|PMID30064364}}

<references/>

==Reference==

Physiology and Pathophysiology of Inner Ear Melanin{{#pmid:3070525|PMID3070525}}

Talk:2018 Group Project 1

2018-10-06T10:44:43Z

2018-10-03T11:29:04Z

Z5229132: /* History */