Practice question

First lineage decision in blastocyst is regulated by differential Hippo signaling based on cell position and polarity. Inner apolar cells activate Lats1/2 kinases, phosphorylate YAP leading to cytoplasmic sequestration and degradation, preventing TEAD activity, thus permitting Oct4 driven inner cell mass specification. Outer polarized cells possess apical domains that inhibit Lats, permitting nuclear YAP accumulation and TEAD-dependent Cdx2 expression specifying trophectoderm. Genetic ablation converting Hippo ON to OFF shifts inner cells toward extra trophectoderm, confirming Hippo promotes ICM fate, suppresses TE program during early embryogenesis and lineage segregation events.