During mammalian embryogenesis, cells must break symmetry in order to undergo cell specification and establish polarity in the embryo. Previously, Claudia Gerri, Kathy Niakan and colleagues have shown that regulation of cell polarity via atypical protein kinase C (aPKC) is a conserved mechanism in trophectoderm (TE) differentiation in mammalian embryos. However, the mechanisms by which cell polarity then informs cell fate, and whether this is conserved across mammals, is not yet known. In this latest study, they now investigate the role of Hippo signalling, which is thought to act downstream of aPKC, in mouse, rat, cow and human embryos. Here, the authors show that inhibition of LATS, the Hippo pathway kinases, results in ectopic TE initiation in all four species, suggesting a conserved mechanism. Interestingly, however, the timing and dynamics of this process differs between species, with rat embryos more closely recapitulating human and cow developmental dynamics compared with mouse. Thus, despite conservation of the underlying molecular players, species-specific differences in lineage specification, most distinctly in the mouse, are present. Together, these findings highlight the importance and conserved role of Hippo signalling during early cell specification in mammalian embryos.
