Wnt and TGF-β signaling are required for the development of Spemann's Organizer in the amphibian dorsal compartment. While transcription factors associated with each pathway translocate to the nucleus to induce specific gene expression in Xenopus, they have not previously been shown to interact with each other. Nishita et al. demonstrate that the expression of the Xtwn gene in Spemann's Organizer, known to be inducible by Lef-1 (an Xwnt-activated transcription factor), is also increased by other factors. The nucleotide sequence of the Xtwn promoter revealed four potential Smad4 binding sites. Injection of embryos with Xwnt8 mRNA revealed that Smad4 nuclear accumulation coincided with nuclear translocation of β-catenin, indicating that Wnt signaling may direct Smad4 into the nucleus. Through coexpression experiments, Nishita et al. determined that Lef-1 can exist in complexes with β-catenin and Smad4. Other experiments revealed that endogenous β-catenin-Smad4 complexes also occurred, as a result of Wnt-dependent increases in the amount of β-catenin. Interaction between β-catenin and Smad4 likely requires the presence of Lef-1, whose HMG box was shown to bind the Smad4 MH1 domain.
Nishita, M., Hashimoto, M.K., Ogata, S., Laurent, M.N., Ueno, N., Shibuya, H., and Cho, K.W.Y. (2000) Interaction between Wnt and TGFβ signaling pathways during formation of Spemann's Organizer. Nature 403: 781-785. [Online Journal]