Notch and Hippo Converge on Cdx2 to Specify the Trophectoderm Lineage in the Mouse Blastocyst

•A Cdx2-enhancer region drives reporter expression in the outer cells of the blastocyst•Notch and Hippo pathways converge on this enhancer to regulate Cdx2•The Notch pathway is activated specifically in the trophectoderm of the blastocyst•Forced expression of Notch drives cells to outer positions and a trophectoderm fate

SummaryThe first lineage choice in mammalian embryogenesis is that between the trophectoderm, which gives rise to the trophoblast of the placenta, and the inner cell mass, from which is derived the embryo proper and the yolk sac. The establishment of these lineages is preceded by the inside-versus-outside positioning of cells in the early embryo and stochastic expression of key transcription factors, which is then resolved into lineage-restricted expression. The regulatory inputs that drive this restriction and how they relate to cell position are largely unknown. Here, we show an unsuspected role of Notch signaling in regulating trophectoderm-specific expression of Cdx2 in cooperation with TEAD4. Notch activity is restricted to outer cells and is able to influence positional allocation of blastomeres, mediating preferential localization to the trophectoderm. Our results show that multiple signaling inputs at preimplantation stages specify the first embryonic lineages.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (266 K)Download as PowerPoint slide