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

   

Authors:	Simon, C. S.; Hur, W.; Garg, V.; Kuo, Y. Y.; Niakan, K. K.; Hadjantonakis, A. K.
Article Title:	ETV4 and ETV5 orchestrate FGF-mediated lineage specification and epiblast maturation during early mouse development
Abstract:	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. © 2025. Published by The Company of Biologists.
Keywords:	signal transduction; dna binding protein; genetics; dna-binding proteins; nonhuman; mouse; animal; cytology; metabolism; animals; mice; mice, knockout; cell maturation; animal experiment; animal model; transcription factor; cell fate; embryo development; embryology; cell differentiation; homeodomain proteins; cell lineage; transcription factors; gene expression regulation; gene expression regulation, developmental; embryo, mammalian; homeodomain protein; body patterning; fibroblast growth factor; fibroblast growth factors; knockout mouse; embryonic development; transcription factor nanog; endoderm; transcription factor ets; mouse embryo; blastocyst; otx transcription factors; transcription factor 4; epiblast; primitive endoderm; inner cell mass; ectoderm; germ layer; proto-oncogene proteins c-ets; fgf; pluripotency; kruppel like factor 5; germ layers; mammalian embryo; female; article; developmental delay; neuronal migration disorder; etv; nanog homeobox protein; etv4 protein, mouse; etv5 protein, mouse; nanog protein, mouse; otx2 protein, mouse; transcription factor otx
Journal Title:	Development (Cambridge)
Volume:	152
Issue:	6
ISSN:	09501991
Publisher:	The Company of Biologists
Date Published:	2025-03-01
Start Page:	dev204278
Language:	English
DOI:	10.1242/dev.204278
PUBMED:	40007475
PROVIDER:	scopus
PMCID:	PMC12050069
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105002056398&doi=10.1242%2fdev.204278&partnerID=40&md5=74d429cfd5889ea6ab0d5c064badf0b9
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Anna-Katerina Hadjantonakis -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/224616