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Cellular localization of the Yes-associated protein (YAP) is dependent on large tumor suppressor (LATS) kinase activity and initiates lineage specification in the preimplantation embryo. We temporally reduced LATS activity to disrupt this early event, allowing its reactivation at later stages. This interference resulted in an irreversible lineage misspecification and aberrant polarization of the inner cell mass (ICM). Complementation experiments revealed that neither epiblast nor primitive endoderm can be established from these ICMs. We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM.

Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation