XENOPUS SMAD7 INHIBITS BOTH THE ACTIVIN AND BMP PATHWAYS AND ACTS AS A NEURAL INDUCER

Smads are proteins that transduce signals on behalf of members of the TGF beta superfamily of growth factors. Recently, inhibitory Smads, Sm ad6, Smad7, and Dad, were isolated from human, mouse, and fly. These a nti-Smads were shown to inhibit TGF beta signaling by stably associati ng to TGF beta type I receptors or, as it was shown for Smad6, by bind ing to receptor-activated Smad1.We report the cloning, distribution, a nd embryological activity of the Xenopus Smad7 (XSmad7). We report tha t XSmad7 inhibits signaling from the activin and BMP pathways in anima l explants although at different thresholds. When expressed in the emb ryo, low concentrations of XSmad7 dorsalize the ventral mesoderm, thus inducing a secondary axis. At higher concentrations however, XSmad7 i nhibits both mesoderm induction and primary axis specification. In add ition, we show that XSmad7 acts as a direct neural inducer both in the context of ectodermal explants and in vivo. We discuss the implicatio ns of these findings in the biochemical context of the activin and BMP pathways as well as their implications in mesodermal, neural, and axi s specification. (C) 1998 Academic Press.