Fig. 2. The first cell lineage decision in the mouse embryo.

While symmetric divisions starting from the 8-cell stage give rise to two outside (green) polarized cells, asymmetric divisions give rise to an outside cell and an inside (grey) apolar cells. In outside cells, TEAD4 transcription factor and its cofactors YAP/WWTR1 regulate the expression of a TE-specific transcription program that ultimately commits outside cells to a trophectoderm fate. This program is not achieved in inside cells because of the activity of the Hippo pathway that leads to the degradation of YAP/WWTR1. ICM cells are not homogenous and an inverse correlation of the expression of Fgf4 and Fgfr2 may presage the divergence between PrE and EPI lineages.