Editing Gastrulation (section)

==Amniotes==

===Overview===
In [[amniote]]s (reptiles, birds and mammals), gastrulation involves the creation of the blastopore, an opening into the [[archenteron]]. Note that the blastopore is not an opening into the [[blastocoel]], the space within the [[blastula]], but represents a new inpocketing that pushes the existing surfaces of the blastula together. In [[amniotes]], gastrulation occurs in the following sequence: (1) the [[embryo]] becomes [[asymmetry|asymmetric]]; (2) the [[primitive streak]] forms; (3) cells from the [[epiblast]] at the [[primitive streak]] undergo an [[Epithelial-mesenchymal transition|epithelial to mesenchymal transition]] and [[ingression (biology)|ingress]] at the [[primitive streak]] to form the [[germ layers]].<ref name=Arnold />

===Symmetry breaking===
In preparation for gastrulation, the embryo must become asymmetric along both the [[Anatomical_terms_of_location#Proximal_and_distal|proximal-distal axis]] and the [[Anatomical terms of location#Axes|anteroposterior axis]]. The proximal-distal axis is formed when the cells of the embryo form the "egg cylinder", which consists of the extraembryonic tissues, which give rise to structures like the [[placenta]], at the proximal end and the [[epiblast]] at the distal end.  Many signaling pathways contribute to this reorganization, including [[bone morphogenetic protein|BMP]], [[fibroblast growth factor|FGF]], [[nodal signaling|nodal]], and [[Wnt signaling pathway|Wnt]]. Visceral endoderm surrounds the [[epiblast]]. The [[Anatomical terms of location#Proximal and distal|distal]] visceral endoderm (DVE) migrates to the [[anterior]] portion of the embryo, forming the [[anterior visceral endoderm]] (AVE). This breaks anterior-posterior symmetry and is regulated by [[NODAL|nodal]] signaling.<ref name=Arnold />
[[File:Epithelial–mesenchymal transition scheme.png|thumb|right|[[Epithelial–mesenchymal transition]] – loss of cell adhesion leads to constriction and extrusion of newly formed [[mesenchymal]] cell.]]

===Germ layer determination===
The [[primitive streak]] is formed at the beginning of gastrulation and is found at the junction between the extraembryonic tissue and the [[epiblast]] on the posterior side of the embryo and the site of [[ingression (biology)|ingression]].<ref name=Tam>Tam & Behringer, 1997</ref> Formation of the [[primitive streak]] is reliant upon [[NODAL|nodal]] signaling<ref name=Arnold /> in the [[Koller's sickle]] within the cells contributing to the primitive streak and [[BMP4]] signaling from the extraembryonic tissue.<ref name=Tam /><ref name=catala2005>Catala, 2005: [https://books.google.com/books?id=RJvkR3gfExwC&pg=PA1535 p. 1535]</ref> Furthermore, [[Cerberus (protein)|Cer1]] and [[Lefty (protein)|Lefty1]] restrict the primitive streak to the appropriate location by antagonizing [[NODAL|nodal]] signaling.<ref name=Loebel>{{cite journal |author1=Tam, P.P.  |author2=Loebel, D.A|title=Gene function in mouse embryogenesis: get set for gastrulation | journal = Nat Rev Genet | volume = 8 | issue = 5 | pages = 368–81 | year = 2007 | pmid = 17387317 | doi = 10.1038/nrg2084|s2cid=138874}}</ref> The region defined as the [[primitive streak]] continues to grow towards the distal tip.<ref name=Arnold />

During the early stages of development, the primitive streak is the structure that will establish [[bilateral symmetry]], determine the site of gastrulation and initiate germ layer formation.<ref>{{Cite journal|last1=Sheng|first1=Guojun|last2=Arias|first2=Alfonso Martinez|last3=Sutherland|first3=Ann|date=2021-12-03|title=The primitive streak and cellular principles of building an amniote body through gastrulation|url=https://www.science.org/doi/abs/10.1126/science.abg1727|journal=Science|volume=374 |issue=6572 |pages=abg1727 |language=EN|doi=10.1126/science.abg1727|pmid=34855481 |s2cid=244841366 |url-access=subscription}}</ref> To form the streak, reptiles, birds and mammals arrange mesenchymal cells along the prospective midline, establishing the first embryonic axis, as well as the place where cells will ingress and migrate during  the process of gastrulation and germ layer formation.<ref name="mikawa">{{cite journal |doi= 10.1002/dvdy.10458 |vauthors=Mikawa T, Poh AM, Kelly KA, Ishii Y, Reese DE |title= Induction and patterning of the primitive streak, an organizing center of gastrulation in the amniote. |journal= Dev Dyn |volume=229 |pages= 422–32|year=2004 |pmid=14991697| issue=3|s2cid=758473 |doi-access=free }}</ref> The primitive streak extends through this midline and creates the antero-posterior body axis,<ref name="downs">{{cite journal |doi= 10.1002/bies.200900038 |author= Downs KM. |title= The enigmatic primitive streak: prevailing notions and challenges concerning the body axis of mammals. |journal= BioEssays |volume=31 |pages= 892–902|year=2009|pmid=19609969| issue=8 |pmc= 2949267}}</ref> becoming the first symmetry-breaking event in the [[embryo]], and marks the beginning of gastrulation.<ref name="chuai">{{cite journal |vauthors=Chuai M, Zeng W, Yang X, Boychenko V, Glazier JA, Weijer CJ |title= Cell movement during chick primitive streak formation. |journal= Dev. Biol. |volume  =296|issue= 1 |pages= 137–49 |year=2006 |pmid=16725136 |pmc= 2556955 |doi= 10.1016/j.ydbio.2006.04.451}}</ref> This process involves the ingression of mesoderm and endoderm progenitors and their migration to their ultimate position,<ref name="downs"/><ref name="chuai M">{{cite book |doi= 10.1016/S0070-2153(07)81004-0 |vauthors=Chuai M, Weijer CJ |chapter=The mechanisms underlying primitive streak formation in the chick embryo. |title=Current Topics in Developmental Biology |volume= 81 |pages= 135–56 |year=2008 |pmid=18023726 |isbn=978-0-12-374253-7}}</ref> where they will differentiate  into the three germ layers.<ref name="mikawa"/> The localization of the cell adhesion and signaling molecule [[beta-catenin]] is critical to the proper formation of the organizer region that is responsible for initiating gastrulation.

===Cell internalization===
In order for the cells to move from the [[epithelium]] of the [[epiblast]] through the [[primitive streak]] to form a new layer, the cells must undergo an [[Epithelial-mesenchymal transition|epithelial to mesenchymal transition]] (EMT) to lose their epithelial characteristics, such as [[Cell adhesion|cell–cell adhesion]]. [[fibroblast growth factor|FGF]] signaling is necessary for proper EMT. [[FGFR1]] is needed for the up regulation of [[SNAI1]], which down regulates [[CDH1 (gene)|E-cadherin]], causing a loss of cell adhesion. Following the EMT, the cells [[ingression (biology)|ingress]] through the [[primitive streak]] and spread out to form a new layer of cells or join existing layers.  [[FGF8]] is implicated in the process of this dispersal from the [[primitive streak]].<ref name=Loebel />