Interaction between Wnt and TGF-beta signalling pathways during formation of Spemann's organizer

Members of the Wnt and TGF-beta superfamilies regulate both cell fate and p roliferation during development and tissue maintenance(1-3). In the early a mphibian embryo, the Wnt and TGF-beta superfamily signalling cascades are r equired for the establishment of a dorsal signalling centre, Spemann's orga nizer(4-8). Intracellular proteins of both pathways, upon activation, trans locate to the nucleus to participate in transcription. Here we show that be ta-catenin and Lef1/Tcf, which are downstream components of the Wnt signall ing cascade, form a complex with Smad4, an essential mediator of signals in itiated by members of the TGF-beta growth factor superfamily. In Xenopus, t his interaction directly and synergistically affects expression of the twin (Xtwn) gene during formation of the organizer. This is, to our knowledge, the first demonstration of a physical interaction between TGF-beta and Wnt signalling components in vivo.