Gastrulation

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.

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, though a bipotential cell population may be derived from mouse embryonic stem cells in vitro.