Interaction between Oct3/4 and Cdx2
determines trophectoderm differentiation
Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, Yagi R and Rossant
J
Cell 123(5):917-29 (2005)
SUMMARY
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.
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