maintains the balance of primitive endoderm versus epiblast specification during mouse embryonic development by suppression of .

The inner cell mass of the mouse blastocyst gives rise to the pluripotent epiblast (EPI), which forms the embryo proper, and the primitive endoderm (PrE), which forms extra-embryonic yolk sac tissues. All inner cells coexpress lineage markers such as and at embryonic day (E) 3.25, and the EPI and PrE precursor cells eventually segregate to exclusively express and , respectively. Fibroblast growth factor (FGF)-extracellular signal-regulated kinase (ERK) signalling is involved in segregation of the EPI and PrE lineages; however, the mechanism involved in regulation is poorly understood. Here, we identified as an upstream repressor of was markedly upregulated in knockout (KO) embryos at E3.0, and was downregulated in embryos overexpressing Furthermore, KO and overexpressing blastocysts showed skewed lineage specification phenotypes, similar to FGF4-treated preimplantation embryos and KO embryos, respectively. Inhibitors of the FGF receptor (Fgfr) and ERK pathways reversed the skewed lineage specification of KO blastocysts. These data demonstrate that suppresses Fgf4-Fgfr-ERK signalling, thus preventing precocious activation of the PrE specification programme.