Fig. 2.

Position-dependent regulation of cell fate in the preimplantation embryo: known and hypothetical mechanisms. Regulation of the Hippo pathway is central to the first cell fate decision. In inside cells, a junctional complex comprised of NF2 and AMOT phosphorylated at S176 activates the Hippo pathway. This leads in turn to the phosphorylation of YAP and TAZ and their exclusion from nuclei, rendering them transcriptionally inactive. In outside cells, apicobasal polarity leads to the sequestration of AMOT dephosphorylated at S176 to the apical domain, resulting in the inactivation of the Hippo pathway. Unphosphorylated YAP is therefore able to go to the nucleus where it can bind to TEAD4 to activate CDX2 transcription and drive TE fate. Other factors, such as mechanical forces, GPCR and PCP signalling may act as cell shape and position sensors and lead to the activation of YAP and TAZ in outside cells principally via modulation of the actin cytoskeleton. Notch signalling, activated in outside cells only via an unknown mechanism, contributes to the transcription of Cdx2 to establish TE fate. TJ: tight junctions. Actin filaments are represented in red. The apical domain of TE cells is outlined in purple and cell–cell junctions are delineated in blue.