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Dev Cell. October 1, 2004; 7 (4): 525-34.

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 .

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.

PubMed ID: 15469841
Article link: Dev Cell.

Genes referenced: act3 actl6a bmp4 cnot2 dvl2 en2 fgf8 hist1h4d mcf2 myc myf5 myod1 nodal nodal1 not otx2 rax rspo1 rspo2 rspo3 shh sox3 t tgfb1 ventx2.2 wnt1 wnt3a wnt8a
Morpholinos referenced: rspo2 MO1

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