R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis

Dev Cell. 2004 Oct;7(4):525-34. doi: 10.1016/j.devcel.2004.07.019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Culture Techniques / methods
  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Luciferases / metabolism
  • Microinjections
  • Molecular Sequence Data
  • Muscle Development*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA / biosynthesis
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction*
  • Trans-Activators
  • Wnt Proteins
  • Xenopus / embryology*
  • Xenopus / genetics
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Rspo2 protein, Xenopus
  • SPON2 protein, human
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • RNA
  • Luciferases

Associated data

  • GENBANK/AY753198
  • GENBANK/AY753199