The timing mechanism for the first lineage specification in the mouse embryo

The transition from totipotency to pluripotency and subsequent differentiation in the mammalian embryo segregates embryonic and extra-embryonic progenitor cells. Despite its central importance, it remains entirely unknown how the timing of this major process is regulated. Here, we uncover that Tfap2c and Tead4 mediated transcriptional activity work in concert with the Rho GTPase mediated activation of actomyosin at the 8-cell stage as the upstream factors that trigger cell polarization and hence the first cell fate segregation in the mouse embryo. We show that they act together to control the establishment of cell polarisation, the activation of polarity dependent Hippo signalling, and the early expression of transcription factors required for the differentiation of the first extra-embryonic lineage. These results define the key step in the transition from totipotency to pluripotency and its relationship to the first cell fate specification event in the mouse embryo. Bulk cell (~80cells) RNA sequencing of embryos injected with dsRNA targeting GFP (control),Tfap2c, Tead4, or Tfap2c and Tead4.