Wnt–TGFβ signalling interaction?

Abstract

Two recent papers suggest that Wnt and TGFβ signalling can interact either synergistically or antagonistically in early Xenopus development. Baker et al.1xWnt signaling in Xenopus embryos inhibits Bmp4 expression and activates neural development. Baker, J.C. et al. Genes Dev. 1999; 31: 3149–3159Crossref | Scopus (239)See all References1 show that, contrary to some earlier reports, Wnt and Wnt signalling components can act as neural inducers in Xenopus embryos. sia and Xnr3 are two genes that are induced by Wnt signalling and have neural-inducing properties. However, when expression of sia and Xnr3 was blocked, using dominant-negative frizzled (a Wnt receptor), neural induction by Wnt was unaffected. By contrast, a dominant-negative version of Tcf (a transcription factor that is activated by Wnt signalling) blocks both responses. This suggests that Wnt can act via alternative pathways, each requiring Tcf.The expression of TGFβ-family member bone morphogenic protein 4 (BMP4) is reduced dorsally during gastrulation, and this was hypothesized to be caused by signals from the dorsal organizer, such as noggin, that block BMP signalling and, hence, self-activation of Bmp expression. However, Baker et al. show that although Wnt and noggin both induce neural tissue, only Wnt represses Bmp4 expression at the gastrula stage. They suggest that β-catenin is increased dorsally, both in the animal hemisphere and in the organizer region, by Wnt signalling that arises from the post-fertilization cortical rotation. This initially induces neural tissue via a decrease in Bmp4 expression, but independently of signals from the organizer, which act later.Nishita et al.2xInteraction between Wnt and TGFβ signalling pathways during formation of Spemann’s organizer. Nishita, M. et al. Nature. 2000; 403: 781–785Crossref | PubMed | Scopus (331)See all References2 demonstrate a direct interaction between components of the Wnt and TGFβ signalling pathways to control the expression of the Xenopus organizer-specific gene twin, a close relative of sia. The twin promoter contains binding sites for the transcription factors lymphoid enhancer binding factor 1 (Lef1) and its relative Tcf, and also for Smads (downstream effectors of TGFβ signalling). Nishita et al. show that Smad4 co-immunoprecipitates with β-catenin and with Lef1. Wnt signalling causes β-catenin to translocate to the nucleus, where it interacts with Lef1 and Tcf. The authors present evidence that Smad4 enters the nucleus along with β-catenin, and that Smad4 and Lef1 and Tcf can co-activate some, but not all Wnt-responsive genes (including twin and sia). They suggest that Wnt and TGFβ could act not only synergistically in this way, but also antagonistically if there is competition for a limited pool of Smad4.