HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst
A) At the 16-cell stage, when ICM progenitors first arise, HIPPO pathway members regulate expression of TE (Cdx2) and ICM (Sox2) genes in parallel. At this stage, OCT4 and NANOG are still expressed ubiquitously. B) In the blastocyst, Sox2 expression is restricted to EPI cells by FGFR/MEK signaling. In EPI cells, SOX2 helps promote expression of Fgf4, which signals to neighboring cells to induce expression of PE genes. In PE cells, MAPK promotes PE gene expression in an Oct4-dependent manner , , , and represses expression of Sox2 and Nanog in PE cells either directly or indirectly. C) In the late blastocyst, SOX2 helps maintain expression of pluripotency genes, and FGF4, or other signals from EPI, maintain expression of PE genes in neighboring cells.