The first cell lineages specified in the mouse embryo are the trophectoderm (TE), which generates the embryonic portion of the placenta, and the inner cell mass (ICM). The ICM subsequently forms the pluripotent epiblast (EPI, which produces the embryo) and the primitive endoderm (PrE, which generates other extra-embryonic structures). Two papers shed new light on these crucially important early embryonic specification events.
On , Janet Rossant and colleagues investigate the role that the intercellular adhesion molecule E-cadherin plays in the divergence of the TE and ICM. By embryonic day 3.5, the TE has formed a polarised epithelial layer that encloses the apolar ICM. The researchers show that the normal epithelial morphology of the TE is disrupted in mouse embryos lacking both maternal and zygotic E-cadherin function but that individual cells in the blastocyst still initiate TE- and ICM-like fates. Interestingly, most of the cells express the TE marker Cdx2, which suggests that organised epithelium formation is not necessary for TE-specific gene expression. Furthermore, individual cells in these embryos still generate an apical membrane domain that correlates with Cdx2 expression. Thus, the epithelial integrity mediated by E-cadherin is not required for Cdx2 expression but is essential for setting normal TE/ICM ratios in mouse embryos.
On , Anna-Katerina Hadjantonakis and colleagues identify a role for platelet-derived growth factor (PDGF) signalling in PrE expansion in mouse embryos. The PDGF receptor α (PDGFRα) is an early marker of the PrE lineage and of extra-embryonic endoderm (XEN) cells, which can be isolated from mouse blastocysts as derivatives of the PrE lineage. By combining live imaging and lineage analysis, the researchers show that Pdgfra expression coincides with that of GATA6, the earliest expressed transcription factor in the PrE lineage. GATA6 expression, they report, is required for Pdgfra transcriptional activation, and PDGF signalling is essential for the establishment and proliferation of XEN cells in culture. Moreover, implantation-delayed Pdgfra-null mutant blastocysts contain reduced PrE cell numbers and, surprisingly, increased EPI cell numbers, indicating that reciprocal signalling between PrE and EPI tissues might regulate compartment size within peri-implantation mammalian embryos. For more on early mouse lineage segregation, see also the review by Lanner and Rossant on .
