Xenopus Smad7 inhibits both the activin and BMP pathways and acts as a neural inducer

Abstract

Smads are proteins that transduce signals on behalf of members of the TGF beta superfamily of growth factors. Recently, inhibitory Smads, Smad6, Smad7, and Dad, were isolated from human, mouse, and fly. These anti-Smads were shown to inhibit TGF beta signaling by stably associating to TGF beta type I receptors or, as it was shown for Smad6, by binding to receptor-activated Smad1. We report the cloning, distribution, and embryological activity of the Xenopus Smad7 (XSmad7). We report that XSmad7 inhibits signaling from the activin and BMP pathways in animal explants although at different thresholds. When expressed in the embryo, low concentrations of XSmad7 dorsalize the ventral mesoderm, thus inducing a secondary axis. At higher concentrations however, XSmad7 inhibits both mesoderm induction and primary axis specification. In addition, we show that XSmad7 acts as a direct neural inducer both in the context of ectodermal explants and in vivo. We discuss the implications of these findings in the biochemical context of the activin and BMP pathways as well as their implications in mesodermal, neural, and axis specification.