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

Nishita, Michiru
Hashimoto, Minako K.
Ogata, Souichi
Laurent, Micheline N.
Ueno, Naoto
Shibuya, Hiroshi
Cho, Ken W. Y.

*Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan
‡Department of Developmental and Cell Biology, University of California, Irvine, California 92617-2300, USA

†These authors contributed equally to this work

§Present address: Department of Biology, California Institute of Technology, 1200E. California Boulevard, Pasadena, California 91125, USA

Received 13 October; accepted 21 December 1999.

Correspondence and requests for materials should be addressed to H.S.

(e-mail: [email protected]) or K.W.Y.C. (e-mail: [email protected]).

Nature 403(6771):p 781-785, February 17, 2000.

Members of the Wnt and TGF-β superfamilies regulate both cell fate and proliferation during development and tissue maintenance. In the early amphibian embryo, the Wnt and TGF-β superfamily signalling cascades are required for the establishment of a dorsal signalling centre, Spemann's organizer. Intracellular proteins of both pathways, upon activation, translocate to the nucleus to participate in transcription. Here we show that β-catenin and Lef1/Tcf, which are downstream components of the Wnt signalling cascade, form a complex with Smad4, an essential mediator of signals initiated by members of the TGF-β growth factor superfamily. In Xenopus, this 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-β and Wnt signalling components in vivo.