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

Nature volume 403, pages 781–785 (2000)Cite this article

Abstract

Members of the Wnt and TGF-β superfamilies regulate both cell fate and proliferation during development and tissue maintenance1,2,3. 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 organizer4,5,6,7,8. 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.

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Figure 1: Deletion analysis of Xtwn reporter genes.
Figure 2: Requirement of Smad4 for Xtwn induction.
Figure 3: Physical interaction and localization of Smad4, Lef1 and β-catenin.
Figure 4: Transcriptional regulation mediated by Smad4, Lef1 and β-catenin.

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Acknowledgements

We thank I. Blitz, M. Waterman and K. Matsumoto for their critical reading of the manuscript and helpful comments; S. Nagai, Y. Takahashi and C. Nugas for assistance; R. Moon, P. ten Dijke, R. Derynck, L. Attisano, O. Tetsu, F. McCormick, J. Thomsen, T. Akiyama, M. Prieve and T. Li for reagents; and L. Raftery for discussion. This work was supported by an NIH grant and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan and ‘Research for the Future’ program of the Japan Society for the promotion of Science.

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Author notes

  1. Micheline N. Laurent

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

  2. Michiru Nishita, Minako K. Hashimoto, Souichi Ogata, Micheline N. Laurent and Ken W. Y. Cho: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki, 444-8585, Japan

    Michiru Nishita, Naoto Ueno & Hiroshi Shibuya

  2. Department of Developmental and Cell Biology, University of California, Irvine, 92617-2300, California , USA

    Minako K. Hashimoto, Souichi Ogata,  Micheline N. Laurent & Ken W. Y. Cho

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Correspondence to Ken W. Y. Cho.

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Nishita, M., Hashimoto, M., Ogata, S. et al. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer. Nature 403, 781–785 (2000). https://doi.org/10.1038/35001602

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