THE DORSALIZING AND NEURAL INDUCING GENE FOLLISTATIN IS AN ANTAGONISTOF BMP-4

Specific signaling molecules play a pivotal role in the induction and specification of tissues during early vertebrate embryogenesis. BMP-4 specifies ventral mesoderm differentiation and inhibits neural inducti on in Xenopus, whereas three molecules secreted from the organizer, no ggin, follistatin and chordin dorsalize mesoderm and promote neural in duction. Here we report that follistatin antagonizes the activities of BMP-4 in frog embryos and mouse teratocarcinoma cells. In Xenopus emb ryos follistatin blocks the ventralizing effect of BMP-4. In mouse P19 cells follistatin promotes neural differentiation. BMP-4 antagonizes the action of follistatin and prevents neural differentiation. In addi tion we show that the follistatin and BMP-4 proteins can interact dire ctly in vitro. These data provide evidence that follistatin might play a role in modulating BMP-4 activity in vivo. (C) 1997 Elsevier Scienc e Ireland Ltd.