Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation.
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.
Niwa
Hitoshi
H
Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan. niwa@cdb.riken.jp
Toyooka
Yayoi
Y
Shimosato
Daisuke
D
Strumpf
Dan
D
Takahashi
Kadue
K
Yagi
Rika
R
Rossant
Janet
J
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099254:Organic Cation Transporter 3
D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000099254:Organic Cation Transporter 3; C487514:Cdx2 protein, mouse; C494174:Pou5f1 protein, mouse