R-Spondin2 is a secreted activator of Wnt/ beta-catenin signaling and is required for Xenopus myogenesis.
We have carried out a small pool expression screen for modulators of the Wnt/ beta-catenin pathway and identified Xenopus R-spondin2 ( Rspo2) as a secreted activator of this cascade. Rspo2 is coexpressed with and positively regulated by Wnt signals and synergizes with Wnts to activate beta-catenin. Analyses of functional interaction with components of the Wnt/ beta-catenin pathway suggest that Rspo2 functions extracellularly at the level of receptor ligand interaction. In addition to activating the Wnt/ beta-catenin pathway, Rspo2 overexpression blocks Activin, Nodal, and BMP4 signaling in Xenopus, raising the possibility that it may negatively regulate the TGF-beta pathway. Antisense Morpholino experiments in Xenopus embryos and RNAi experiments in HeLa cells reveal that Rspo2 is required for Wnt/ beta-catenin signaling. In Xenopus embryos depleted of Rspo2, the muscle markers myoD and myf5 fail to be activated and later muscle development is impaired. Thus, Rspo2 functions in a positive feedback loop to stimulate the Wnt/ beta-catenin cascade.[1]References
- R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Kazanskaya, O., Glinka, A., del Barco Barrantes, I., Stannek, P., Niehrs, C., Wu, W. Dev. Cell (2004) [Pubmed]
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