SMAD7 INHIBITS MESODERM FORMATION AND PROMOTES NEURAL CELL FATE IN XENOPUS EMBRYOS

We report the isolation and characterization of a new inhibitory Smad in Xenopus, which we have designated as Xenopus Smad7. Smad7 is presen t at fairly constant levels throughout early development and at blastu la stages enriched in the ventral side of the animal hemisphere. The i nduction of mesoderm by TGF-beta-like signals is mediated by receptor ALK-4 and we show that Smad7 blocks signaling of ALK-4 in a graded fas hion: lower levels of Smad7 block activation of dorsal mesoderm genes and higher levels block all mesoderm genes expression. Smad7 is able t o directly activate neural markers in explants in the absence of mesod erm or endoderm. This neural-inducing activity of Smad7 may be due to inhibition of BMP-4 signaling because Smad7 can also block BMP-4-media ted mesoderm induction. Thus, Smad7 acts as a potent inhibitor of meso derm formation and also activates the default neural induction pathway . (C) 1998 Academic Press.