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==Molecular regulation of somite differentiation== Surrounding structures such as the notochord, neural tube, epidermis and lateral plate mesoderm send signals for somite differentiation<ref name="RFB2004Mesoderm" /><ref name="Langman's Medical Embryology 2010" /> Notochord protein accumulates in presomitic mesoderm destined to form the next somite and then decreases as that somite is established. The notochord and the neural tube activate the protein SHH, which helps the somite to form its sclerotome. The cells of the sclerotome express the protein PAX1 that induces the cartilage and bone formation. The neural tube activates the protein WNT1 that expresses PAX 2 so the somite creates the myotome and dermatome. Finally, the neural tube also secretes neurotrophin 3, so that the somite creates the dermis. Boundaries for each somite are regulated by [[retinoic acid]] and a combination of FGF8 and WNT3a.<ref name="RFB2004Mesoderm" /><ref name="Langman's Medical Embryology 2010" /><ref name="Cunningham and Duester">{{Cite journal |last=Cunningham |first=T.J. |last2=Duester |first2=G. |date=2015 |title=Mechanisms of retinoic acid signalling and its roles in organ and limb development |journal=Nat. Rev. Mol. Cell Biol. |volume=16 |issue=2 |pages=110β123 |doi=10.1038/nrm3932 |pmc=4636111 |pmid=25560970}}</ref> So retinoic acid is an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation and controls [[bilateral symmetry]] in vertebrates. The bilaterally symmetric body plan of vertebrate embryos is obvious in somites and their derivates, such as the vertebral column. Therefore, asymmetric somite formation correlates with a left-right desynchronization of the segmentation oscillations.<ref>{{Cite journal |last=Vermot |first=J. |last2=Gallego Llamas |first2=J. |last3=Fraulob |first3=V. |last4=Niederreither |first4=K. |last5=Chambon |first5=P. |last6=DollΓ© |first6=P. |date=April 2005 |title=Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo |url=https://authors.library.caltech.edu/51934/7/Vermot.SOM.pdf |url-status=live |journal=Science |volume=308 |issue=5721 |pages=563β566 |bibcode=2005Sci...308..563V |doi=10.1126/science.1108363 |pmid=15731404 |s2cid=5713738 |archive-url=https://ghostarchive.org/archive/20221009/https://authors.library.caltech.edu/51934/7/Vermot.SOM.pdf |archive-date=2022-10-09}}</ref> Many studies with ''Xenopus'' and zebrafish have analyzed the factors of this development and how they interact in signaling and transcription. However, there are still some doubts in how the prospective mesodermal cells integrate the various signals they receive and how they regulate their morphogenic behaviours and cell-fate decisions.<ref name="Yusuf-2006" /> Human embryonic stem cells for example have the potential to produce all of the cells in the body and they are able to self-renew indefinitely so they can be used for a large-scale production of therapeutic cell lines. They are also able to remodel and contract collagen and were induced to express muscle actin. This shows that these cells are multipotent cells.<ref>{{Cite journal |last=Boyd |first=N.L. |last2=Robbins KR |first2=K.R. |last3=Dhara SK |first3=S.K. |last4=West FD |first4=F.D. |last5=Stice SL. |first5=S.L. |date=August 2009 |title=Human embryonic stem cell-derived mesoderm-like epithelium transitions to mesenchymal progenitor cells |journal=Tissue Engineering. Part A |volume=15 |issue=8 |pages=1897β1907 |doi=10.1089/ten.tea.2008.0351 |pmc=2792108 |pmid=19196144}}</ref>
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