Development 1999 Dec 01;12624:5621-34. doi: 10.1242/dev.126.24.5621.

FAST-1 is a key maternal effector of mesoderm inducers in the early Xenopus embryo.

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We have examined the role of the maternally encoded transcription factor FAST-1 in the establishment of the mesodermal transcriptional program in Xenopus embryos. FAST-1 has been shown to associate with Smad2 and Smad4, transducers of TGFbeta superfamily signals, in response to stimulation by several TGFbeta superfamily ligands. The FAST-1/Smad2/Smad4 complex binds and activates a 50 bp activin responsive element identified in the promoter of the meso-endodermal marker Mix.2. We have now used three complementary approaches to demonstrate that FAST-1 is a central regulator of mesoderm induction by ectopic TGFbeta superfamily ligands and during endogenous patterning: ectopic expression of mutationally activated FAST-1, ectopic expression of dominant inhibitory FAST-1, and injection of a blocking antibody specific for FAST-1. Expression of constitutively transcriptionally active FAST-1 fusion protein (FAST-VP16(A)) in prospective ectoderm can directly induce the same set of general and dorsal mesodermal genes, as well as some endodermal genes, as are induced by activin or Vg1. In intact embryos, this construct can induce secondary axes similar to those induced by activin or Vg1. Conversely, expression of a FAST-1-repressor fusion (FAST-En(R)) in prospective ectoderm blocks induction of mesodermal genes by activin, while expression of FAST-En(R) in intact embryos prevents general/dorsal mesodermal gene expression and axial development. Injection of a blocking antibody specific for FAST-1 prevents induction of mesodermal response genes by activin or Vg1, but not by FGF. In intact embryos, this antibody can prevent the expression of early mesodermal markers and inhibit axis formation, demonstrating that FAST-1 is a necessary component of the first steps in the specification of mesoderm.

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Species referenced: Xenopus
Genes referenced: foxh1 gdf1 smad10 smad2 smad4 tgfb1
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