Table 1.

Selected transcription factors implicated in TE and PE differentiation

Name	Initial expression	Localization	Loss-of-function phenotype	Gain-of-function phenotype	References
TE-specific transcription factors
Cdx2	Evidence for maternal mRNA; protein detected at 8-cell stage	Restricted to TE at E3.5; ubiquitous before 32-cell stage	Zygotic mutant: TE develops, but dies; TE expresses ICM markers; siRNA of maternal and zygotic transcripts; variable results	Expression in ES cells induces TS cell differentiation	Niwa et al. 2005; Strumpf et al. 2005; Dietrich and Hiiragi 2007; Ralston and Rossant 2008; Jedrusik et al. 2010; Wu et al. 2010
Tead4	mRNA detectable at 2- to 4-cell stage; protein at ∼4-cell stage	Ubiquitous throughout preimplantation	Zygotic mutant: loss of Cdx2 expression after 8-cell stage; ectopic ICM markers in surface cells; failure to form blastocyst	Expression of Tead4 DNA-binding domain fused to VP16 transcriptional activation domain in ES cells induces TS cell differentiation	Yagi et al. 2007; Nishioka et al. 2008, 2009
Yap1 (Wwtr1 is similar to Yap)	mRNA and nuclear protein detectable from 4-cell stage	Nuclear-localized in outer cells; cytoplasmic in inner cells (Wwtr1 does not appear to have cytoplasmic distribution in inner cells)	Dominant-negative Yap expression leads to reduced Cdx2 expression	Overexpression in inner cells of blastocyst induces Cdx2 expression	Nishioka et al. 2009
Eomes	Protein undetectable until blastocyst stage	Restricted to TE	Zygotic mutant: form TE that expresses Cdx2, but fail to implant, and TE fails to differentiate	Expression in ES cells induces TS cell differentiation, but TS cells require Cdx2 expression for maintenance	Niwa et al. 2005; Strumpf et al. 2005; Ralston and Rossant 2008
Gata3	mRNA detected at low levels at 1-cell stage; protein detected at late 8-cell stage	Restricted to TE at E3.5; ubiquitous before this	Zygotic mutants have postimplantation phenotype with placental defects; shRNA knockdown leads to failure to form expanded blastocyst and reduced Cdx2 expression	Expression in ES cells induces TS cell differentiation and XEN-like (primitive endoderm-like cells) differentiation	Ma et al. 1997; Ralston and Rossant 2008; Home et al. 2009; Nishiyama et al. 2009
Klf5	Nuclear protein detectable at 2-cell stage	Ubiquitous early; strong in TE, weak in ICM of blastocysts	Rarely forms blastocyst; loss of Cdx2 expression, but still get repression of ICM markers in TE	Overexpression in blastocysts partially represses endoderm fate; expression in ES cells maintains LIF-independent self-renewal; expression with cofactors can dedifferentiate fibroblasts into ES-like cells	Nakagawa et al. 2008; Niwa et al. 2009; Lin et al. 2010
Primitive endoderm-specific transcription factors
Gata4	Nuclear Gata4 protein detectable in ∼64-cell embryos	Restricted to PE at E4.5	Postimplantation phenotype; loss of visceral endoderm differentiation in Gata4-null embryoid bodies	Expression in ES cells induces XEN-like differentiation	Soudais et al. 1995; Fujikura et al. 2002; Shimosato et al. 2007; Plusa et al. 2008
Gata6	Protein detectable in some 4-cell embryos	Ubiquitous early; mosaic in ICM at E3.5; restricted to PE at E4.5	Postimplantation phenotype; embryos are growth retarded and show defects in extraembryonic endoderm gene expression	Expression in ES cells induces XEN-like differentiation	Morrisey et al. 1998; Fujikura et al. 2002; Chazaud et al. 2006; Shimosato et al. 2007
Sox17	mRNA initiated at 8-cell to blastocyst stage; protein observed at morula stage	Expression mosaic in early blastocyst; restricted to PE at E4.5	Postimplantation phenotype; delayed embryos with defects in visceral and definitive endoderm	Overexpression in ES cells induces extraembryonic gene expression	Kanai-Azuma et al. 2002; Kim et al. 2007; Niakan et al. 2010

Transcription factors are divided into sections appropriate to the tissue in which they appear to function.