Inhibition of Excess Nodal Signaling During Mouse Gastrulation by the Transcriptional Corepressor DRAP1

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Science  06 Dec 2002:
Vol. 298, Issue 5600, pp. 1996-1999
DOI: 10.1126/science.1073405

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The formation and patterning of mesoderm during mammalian gastrulation require the activity of Nodal, a secreted mesoderm-inducing factor of the transforming growth factor–β (TGF-β) family. Here we show that the transcriptional corepressor DRAP1 has a very specific role in regulation of Nodalactivity during mouse embryogenesis. We find that loss ofDrap1 leads to severe gastrulation defects that are consistent with increased expression of Nodal and can be partially suppressed by Nodal heterozygosity. Biochemical studies indicate that DRAP1 interacts with and inhibits DNA binding by the winged-helix transcription factor FoxH1 (FAST), a critical component of a positive feedback loop for Nodal activity. We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop.

  • * These authors contributed equally to this work.

  • Present address: Institute Albert Bonniot, Domaine de la Merci, 38706 La Tronche Cedex, France.

  • Present address: Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

  • § To whom correspondence should be addressed. E-mail: reinbedf{at}, mshen{at}

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