Gene function in mouse embryogenesis: get set for gastrulation

At the time of implantation, the mouse embryo consists of three cell lineages: the trophectoderm, the primitive endoderm and the epiblast. The primitive endoderm forms from Gata6-expressing cells that are scattered throughout the inner cell mass. Its formation requires the action of a transcriptional network and sorting of cells, which is mediated by growth factor receptor bound protein 2 (GRB2) and mitogen-activated protein kinase (MAPK) activities.The extraembryonic ectoderm, derived from the trophectoderm, is maintained by the interaction of nodal and FGF signals that originate in the epiblast. The visceral endoderm, which derives from the primitive endoderm, is initially regionalized in a proximal–distal manner by the action of nodal signalling. Some recent data indicate that asymmetry might be present in the primitive endoderm soon after it forms, but this is controversial.The formation of the distal visceral endoderm requires interactions with the epiblast and extraembryonic ectoderm, through the actions of nodal, WNT and bone morphogenetic protein 4 (BMP4) signalling.Formation of the primitive streak and the initiation of gastrulation require correct anterior–posterior patterning of the epiblast. This is achieved by a balance of posteriorizing signals (WNT, nodal and BMP) and their antagonists, which are produced in the anterior visceral endoderm.Migration of the distal visceral endoderm to the anterior part of the embryo is driven by asymmetrical cell proliferation, which is affected by nodal and its antagonists along with active cell migration, and modulated by the level of WNT signals.The formation of the mesoderm and definitive endoderm requires migration of cells through the primitive streak. This requires FGF signalling, which influences WNT signalling. Correct migration of the mesoderm and endoderm requires the actions of the transcription factors that are encoded by Lhx1 and Mixl1.The choice of cells in the primitive streak to follow either a mesoderm or a definitive endoderm fate is influenced by the signalling activity of transforming growth factor-β (TGFB)-related factors and WNT. Loss of gene activity downstream of nodal signalling results in reduced potential to form endoderm.