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

Abstract

Members of the Wnt and TGF-beta superfamilies regulate both cell fate and proliferation during development and tissue maintenance. In the early amphibian embryo, the Wnt and TGF-beta 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 beta-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-beta 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-beta and Wnt signalling components in vivo.

Smad1, β-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription

“…Consistent with this finding is the recognition that Bmp2 induces recruitment of LEF1/Tcf to the promoter, association of Lef1/Tcf with the SBE and association of Smad1 with the TBE. Molecular interactions between Smad and β-catenin effectors during normal embryogenesis have been observed between Smad4 and Lef1/Tcf and between Smad4 and β-catenin in Xenopus, specifically involving cooperative interactions between Smad4 and Lef1/Tcf at the Xtwn promoter (Nishita et al, 2000). The nature of these interactions has been further elucidated in genetic cell models.…”

Development of the upper lip: Morphogenetic and molecular mechanisms

“…Amand et al, 2000). The Smad proteins in the Tgf␤/Bmp signaling pathway have been found to directly interact with Tcf/Lef proteins, transcription factors of the Wnt/␤-catenin pathway (Nishita et al, 2000). Fgf signaling has been shown to induce phosphorylation of GSK3␤ and influence the stability and nuclear entry of ␤-catenin in a cell-type dependent manner (Torres et al, 1999;Israsena et al, 2004).…”

Regulation of cell proliferation by Smad proteins

“…TGF-b stimulation triggers the interaction between Smads and AML1 and their binding to the IgA promoter, upon which the IgA promoter is activated Zhang and Derynck, 2000). Smad4 was found to interact and functionally cooperate with b-catenin and LEF1/TCF, which are downstream components of the Wnt signaling pathway, in inducing Xenopus twin (Xtwn) gene expression (Nishita et al, 2000). Smad3 has also been reported to functionally interact with LEF1/TCF in a TGF-bdependent manner independent of b-catenin (Labbe  et al, 2000).…”