ETV4 and ETV5 Orchestrate FGF-Mediated Lineage Specification and Epiblast Maturation during Early Mouse Development

Abstract

AbstractCell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signaling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factorsEtv4andEtv5are critical mediators of FGF signaling in cell lineage specification and maturation in mouse embryos. We show that loss ofEtv5compromises primitive endoderm formation at pre-implantation stages. Furthermore,Etv4/5deficiency delays naïve pluripotency exit and epiblast maturation, leading to elevated NANOG and reduced OTX2 expression within the blastocyst epiblast. As a consequence of delayed pluripotency progression,Etv4/5deficient embryos exhibit anterior visceral endoderm migration defects post-implantation, a process essential for coordinated embryonic patterning and gastrulation initiation. Our results demonstrate the successive roles of these FGF signaling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development.Summary statementFGF signaling effectors ETV4/5 regulate lineage specification and embryo patterning in mice, affecting primitive endoderm formation and pluripotency exit.