HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo.

During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of , the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress while promoting expression of the trophectoderm gene in parallel.