R-Spondin2 Is a Secreted Activator of Wnt/β-Catenin Signaling and Is Required for Xenopus Myogenesis
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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.
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Norrin and R-Spondin2 can bind to the LRP5/6 receptor and may activate Wnt signaling independent of a Wnt ligand.
“An interesting recent finding is the identification of factors including Norrin23 and R-Spondin2,24 which can bind to the LRP5/6 receptor and may activate Wnt signaling independent of a Wnt ligand.”
From Wnt signal transduction pathways (2008) · cites this paper as [24]
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- Authors
- Kazanskaya, O., Glinka, A., del Barco Barrantes, I., Stannek, P., Niehrs, C., & Wu, W.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Niehrs, Christof
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 7
- Issue
- 4
- Pages
- 525-534
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2018602900
- Cited by
- 431
- References
- 46
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 19 · 2023: 11 · 2022: 20 · 2021: 20 · 2020: 35 · 2019: 19 · 2018: 26 · 2017: 23 · 2016: 23 · 2015: 16 · 2014: 25 · 2013: 26 · 2012: 33
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- RSPO2, Wnt/β-catenin signaling, myogenesis, Xenopus, activin signaling, Nodal signaling, BMP4 signaling, TGF-beta signaling, MyoD, Myf5, positive feedback loop, ligand-receptor interactions
- MeSH terms
- Animals, Cell Line, Cytoskeletal Proteins, HeLa Cells, Humans, Immunohistochemistry, Luciferases, Microinjections, Molecular Sequence Data, Neoplasm Proteins, Proto-Oncogene Proteins, Recombinant Proteins, RNA, Xenopus, Blotting, Western, Signal Transduction, Trans-Activators, Extracellular Matrix Proteins, In Situ Hybridization, Genes, Reporter, Muscle Development, Xenopus Proteins, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Culture Techniques, Wnt Proteins, beta Catenin
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