ETV4 and ETV5 orchestrate FGF-mediated lineage specification and epiblast maturation during early mouse development.

Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signalling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors Etv4 and Etv5 are crucial mediators of FGF signalling in cell lineage specification and maturation in mouse embryos. We show that loss of Etv5 compromises primitive endoderm formation at pre-implantation stages. Furthermore, Etv4 and Etv5 (Etv4/5) deficiency 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/Etv5-deficient 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 signalling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development.