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Homo sapiens
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Gastrulation is the reorganization of the blastula to form the multilayered gastrula. During gastrulation, a portion of cells from the exterior of the epithelial epiblast layer migrate to the interior, where they form mesoderm and endoderm which, together with the outer layer of ectoderm (arising from epiblast cells that have not migrated), comprise the three cell layers that are characteristic of triploblastic metazoans (reviewed in Technau and Scholz 2003). In the human peri-implantation embryo, epiblast cells ingress through the primitive streak located in the posterior region of the embryonic disc to form the mesoderm and endoderm of the embryo proper (reviewed in Bardot and Hadjantonakis 2020, Ghimire et al. 2021, Zhai et al. 2021, Rossant and Tam 2022). In the mouse, a mammalian model organism, the embryo is cup-shaped instead of being disc-shaped (reviewed in Kojima et al. 2014). However, the morphogenetic process of germ layer formation is broadly conserved in both species.
The primitive streak forms at the posterior region of the epiblast where there is high signaling activity of NODAL, BMP, FGF and WNT pathways, which drive the allocation of cells to the mesoderm and endoderm lineages. In the primitive streak, the ingressing cells undergo epithelial-to-mesenchymal transition (reviewed in Amack 2021). Cells allocated to the mesoderm acquire a mesenchymal phenotype. Endodermal cells are reputed to revert back to an epithelial architecture through a mesenchymal-to-epithelial transition as they are integrated into the pre-existing layer of hypoblast. A recent study in mouse, however, revealed that ingressing cells that are destined for the endoderm undergo an incomplete or partial-EMT and retain some epithelial features prior to re-acquiring epithelialization (Scheibner et al. 2021).
During gastrulation in mice, extraembryonic mesoderm is formed first and is followed by mesoderm that populates the anterior structures, the head, face and heart of the embryo and next the mesoderm to the trunk. Endoderm is also formed in an anterior to posterior sequence, with endoderm emerging early in gastrulation populating the foregut, followed by the mid- and hind-gut. Along the anterior-posterior axis of the primitive streak, endoderm and axial mesoderm emerge from the anterior region, whereas mesoderm emerging from the mid- to posterior regions is allocated in a medial-lateral order to paraxial, intermediate and lateral plate mesoderm. Cells remaining in the overlying epiblast contribute to the ectoderm. Cells of the ectoderm are allocated to the neural ectoderm and to the surface ectoderm and the neural border cells that give rise to the neural crest cells. Patterning of the neuroectoderm is facilitated by the inductive interaction with prechordal plate and the notochord derived from the axial mesoderm.
Before ingression, cells of the primitive streak express genes such as TBXT (T, BRACHYURY) and EOMES that are characteristic of nascent mesoderm and endoderm. It is not known if there are common progenitors that give rise to all types of mesodermal derivatives, such as lateral plate mesoderm and paraxial mesoderm. The knowledge to this date indicates that the different types of mesodermal derivatives are allocated in accordance to the timing and locality of emergence from the primitive streak. The existence of bipotential mesendoderm progenitors in the gastrulating embryo is unresolved but unlikely (Probst et al. 2021), though a bipotential cell population may be derived from mouse embryonic stem cells in vitro.

Literature References
PubMed ID Title Journal Year
24954643 Timing of developmental events in the early mouse embryo

Tam, OH, Kojima, Y, Tam, PPL

Semin Cell Dev Biol 2014
34417090 Human embryonic development: from peri-implantation to gastrulation

Xiao, Z, Wang, Y, Wang, H, Zhai, J

Trends Cell Biol 2021
34168324 Epithelial cell plasticity drives endoderm formation during gastrulation

Böttcher, A, Ansarullah, A, Lickert, H, Cernilogar, FM, Beckers, J, Sterr, M, Burtscher, I, Büttner, M, Schotta, G, Scheibner, K, Theis, FJ, Schirge, S, Irmler, M, Yang, D

Nat Cell Biol 2021
35077679 Early human embryonic development: Blastocyst formation to gastrulation

Rossant, J, Tam, PPL

Dev Cell 2022
34294089 Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development

Amack, JD

Cell Commun Signal 2021
32473204 Mouse gastrulation: Coordination of tissue patterning, specification and diversification of cell fate

Hadjantonakis, AK, Bardot, ES

Mech Dev 2020
14756329 Origin and evolution of endoderm and mesoderm

Scholz, CB, Technau, U

Int J Dev Biol 2003
33484705 Human gastrulation: The embryo and its models

Moris, N, Martinez Arias, A, Ghimire, S, Mantziou, V

Dev Biol 2021
33199445 Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation

Grün, D, Schwan, C, Probst, S, Tosic, J, Arnold, SJ, Sagar, S

Development 2021
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