Editing Neural plate (section)

==Development==

During the stage of neural plate formation the embryo consists of three [[Germ layer|cell layers]]: the [[ectoderm]] that eventually forms the skin and neural tissues, the [[mesoderm]] that forms muscle and bone, and the [[endoderm]] that will form the cells lining the digestive and respiratory tracts. The progenitor cells that make up the precursors to neural tissues in the neural plate are called [[neuroepithelial cells]].{{cn|date=October 2023}}

Stretched over the [[notochord]], the ectodermal cells on the dorsal portion of the embryo are ultimately the ones that form the neural plate.  Approximately half of those cells will be induced to remain ectoderm, while the other half will form the neural plate.<ref name=Browder>{{cite book|last=Browder|first=Leon|title=Developmental Biology|year=1980|publisher=Saunders College|location=Philadelphia|isbn=0-03-056748-3|page=[https://archive.org/details/developmentalbio00brow/page/457 457]|url-access=registration|url=https://archive.org/details/developmentalbio00brow/page/457}}</ref><ref name="Module 7">Human Embryology, Module 7, Section 7.2, http://www.embryology.ch/anglais/hdisqueembry/triderm10.html {{Webarchive|url=https://web.archive.org/web/20130116004631/http://www.embryology.ch/anglais/hdisqueembry/triderm10.html |date=2013-01-16 }}.</ref>

There are four stages of neural plate and neural tube formation: formation, bending, convergence, and closure.
The formation of the neural plate starts when dorsal mesoderm signals ectodermal cells above it to lengthen into columnar neural plate cells.<ref>{{cite journal|last=Keller|first=Ray|author2=Shih, John |author3=Sater, Amy K |title=Planar induction of convergence and extension of the neural plate by the organizer Xenopus|journal=Developmental Dynamics|date=1 March 1992|volume=193|issue=3|pages=218–234|doi=10.1002/aja.1001930303|pmid=1600241|s2cid=39722561}}</ref> This different shape distinguishes the cells of the presumptive neural plate from other pre-epidermal cells. If the neural plate is separated by itself, it will still develop to make a thinner plate but will not form a neural tube. If the region containing presumptive epidermis and neural plate tissue is isolated, small [[neural fold]]s will form. Elongation that occurs throughout the formation of the neural plate and closure of the neural tube is vital; the closing areas of the neural tube
are seen to have very increased elongation activity in the midline compared to already closed areas when the plate was beginning to shape itself into a tube.<ref name="Jacobson"/>

[[File:Gray648.png|thumb|Bending and Convergence of the Neural Plate]]

The bending of the neural plate involves the formation of hinges, where the neural plate is connected to surrounding tissues. The midline of the neural plate is referred to the median hinge point (MHP). Cells in this area, known as medial hinge point cells because of their involvement with this structure, are stabilized and connected to the notochord. They are derived from the area of the neural plate anterior to primitive knot. The notochord will begin the shape changes in MHP cells. These cells will decrease in height and become wedge-shaped. Another type of hinge point occurs dorsal-laterally, referred to as dorsal-lateral hinge point (DLHP). These regions furrow and change shape in the same way as MHP cells do before connecting together to form the neural tube. It was seen in an experiment that without the notochord, the MHP characteristics did not develop correctly, so the neural plate and neural tube formation did not happen properly.<ref>{{cite journal|last=Smith|first=Jodi L.|author2=Schoenwolf, Gary C.|title=Notochordal induction of cell wedging in the chicken neural plate and its role in neural tube formation|journal=Journal of Experimental Zoology|date=1 April 1989|volume=250|issue=1|pages=49–62|doi=10.1002/jez.1402500107|pmid=2723610}}</ref> The communication between the neural plate and the [[notochord]] is important for the future induction and formation of the neural tube.

Closure of the neural tube is completed when the neural folds are brought together, adhering to each other.  While the cells that remain as the neural tube form the brain and spinal cord, the other cells that were part of the neural plate migrate away from the tube as neural crest cells.  After an [[epithelial–mesenchymal transition]], these cells form the [[autonomic nervous system]] and certain cells of the [[peripheral nervous system]].<ref name=Wolpert>{{cite book|last=Wolpert|first=Lewis|title=Principles of Development|year=1998|publisher=Current Biology|location=London|isbn=0-19-850263-X|page=345}}</ref>

===Cell signaling and essential proteins===

Critical to the proper folding and function of the neural plate is N-cadherin, a type of [[cadherin]] protein associated with the nervous system.  N-cadherin is critical to holding neural plate cells together.  Additionally, cells destined to become neural plate cells express nerve cell adhesion molecule (NCAM) to further neural plate cohesion.  Another cadherin, E-cadherin, is expressed by ectodermal cells in the process of neural plate development.<ref name="Gilbert" />

[[File:Protein BMP4 PDB 1reu.png|thumb| 3-D structural model of [[Bone morphogenetic protein 4|BMP-4]]]]
[[Bone morphogenetic protein 4]], or BMP4, is a transforming growth factor that causes the cells of the ectoderm to differentiate into skin cells. Without BMP4 the ectoderm cells would develop into neural cells.  [[Reflection symmetry|Axial]] mesoderm cells under the ectoderm secrete inhibitory signals called [[chordin]], [[Noggin (protein)|noggin]] and [[follistatin]].  These inhibitory signals prevent the action of BMP4, which would normally make the cells ectoderm; as a result, the overlying cells take their normal course and develop into neural cells.  The cells in the ectoderm that circumscribe these neural cells do not receive the BMP4 inhibitor signals and as a result BMP4 induces these cells to develop into skin cells.<ref>{{cite journal|last=Wilson|first=PA|author2=Lagna, G |author3=Suzuki, A |author4= Hemmati-Brivanlou, A |title=Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1.|journal=Development|date=Aug 1997|volume=124|issue=16|pages=3177–84|doi=10.1242/dev.124.16.3177 |pmid=9272958}}</ref>

Neural plate border specifiers are induced as a set of transcription factors. Distalless-5, [[PAX3]] and [[PAX7]] prevent the border region from becoming either neural plate or epidermis.<ref name="Gilbert" /> These induce a second set of transcription factors called neural crest specifiers, which cause cells to become [[neural crest cells]].

In a newly formed neural plate, PAX3 mRNA, [[MSX1]] mRNA, and MSX1/MSX2 proteins are expressed mediolaterally.<ref name=Liem>{{cite journal|last=Liem|first=Karel F|author2=Tremml, Gabi |author3=Roelink, Henk |author4= Jessell, Thomas M |title=Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm|journal=Cell|date=1 September 1995|volume=82|issue=6|pages=969–979|doi=10.1016/0092-8674(95)90276-7|pmid=7553857|s2cid=17106597|doi-access=free}}</ref>  When the neural plate begins to fold, rostral areas of the neural plate do not express Pax3 and MSX proteins. Areas caudal to [[neural tube]] closure have PAX3 and MSX expression restricted to lateral regions of the neural folds.<ref name="Liem" /> These fluctuations in mRNA and protein expression allude to how they play a role in differentiation of neural plate cells.

Low pSMAD 1, 5, 8 levels allow a greater mobility at the median hinge point than in lateral neural plate cells.<ref>{{cite journal|last=Eom|first=Dae S|author2=Amarnath, Smita |author3=Agarwala, Seema |title=Apicobasal Polarity and neural tube closure|journal=Development, Growth & Differentiation|date=20 December 2012|volume=55|issue=1|pages=164–172|doi=10.1111/dgd.12030|pmid=23277919|pmc=3540145}}</ref> This flexibility allows for the pivoting and hinging that allows the buckling and lifting of the neural plate when formatting the neural tube. The neural plate has to be rigid enough for morphogenic movements to occur while being flexible enough to undergo shape and position changes for the transformation to the neural tube.