RRC ID 28452
Author Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, Yagi R, Rossant J.
Title Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation.
Journal Cell
Abstract Trophectoderm (TE), the first differentiated cell lineage of mammalian embryogenesis, forms the placenta, a structure unique to mammalian development. The differentiation of TE is a hallmark event in early mammalian development, but molecular mechanisms underlying this first differentiation event remain obscure. Embryonic stem (ES) cells can be induced to differentiate into the TE lineage by forced repression of the POU-family transcription factor, Oct3/4. We show here that this event can be mimicked by overexpression of Caudal-related homeobox 2 (Cdx2), which is sufficient to generate proper trophoblast stem (TS) cells. Cdx2 is dispensable for trophectoderm differentiation induced by Oct3/4 repression but essential for TS cell self-renewal. In preimplantation embryos, Cdx2 is initially coexpressed with Oct3/4 and they form a complex for the reciprocal repression of their target genes in ES cells. This suggests that reciprocal inhibition between lineage-specific transcription factors might be involved in the first differentiation event of mammalian development.
Volume 123(5)
Pages 917-29
Published 2005-12-2
DOI 10.1016/j.cell.2005.08.040
PII S0092-8674(05)00911-6
PMID 16325584
MeSH Animals Blastocyst* / cytology Blastocyst* / physiology CDX2 Transcription Factor Cell Differentiation / physiology* Cell Lineage* Cells, Cultured Enzyme Activation Gene Expression Regulation, Developmental Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Mice Mice, Inbred C57BL Octamer Transcription Factor-3 / genetics Octamer Transcription Factor-3 / metabolism* Organic Cation Transport Proteins / genetics Organic Cation Transport Proteins / metabolism* Pluripotent Stem Cells / cytology Pluripotent Stem Cells / physiology* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism*
IF 36.216
Times Cited 750
DNA material pCdx2p-luc (RDB07098) pPyCAG-EGFP-IZ (RDB08526) pPyCAG-Cdx2ER-IP (RDB10265).