ArticleNature communications2020
R-spondins are BMP receptor antagonists in Xenopus early embryonic development.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- Label-free photoacoustic imaging of glassfrog development.Photoacoustics · 2025Article
- WNK kinase regulates plasma membrane levels of the WNT inhibitor RNF43: A WNK-RNF43 circuit regulates WNT signal suppression.bioRxiv : the preprint server for biology · 2025Article
- "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025Article
- RSPO2 Coordinates with GDF9:BMP15 Heterodimers to Promote Granulosa Cell and Oocyte Development in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- [Role of R-spondin 2 on osteogenic differentiation of bone marrow mesenchymal stem cells and bone metabolism in ovariectomized mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells.Biomedicines · 2024Review
- Article
- Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/β-catenin signaling.American journal of human genetics · 2024Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient.Nature communications · 2024Article
- Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing.Bone · 2023Article
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- Article
- Bmp4 Synexpression Gene,International journal of molecular sciences · 2022Article
- Feedback Regulation of Signaling Pathways for Precise Pre-Placodal Ectoderm Formation in Vertebrate Embryos.Journal of developmental biology · 2022Review
- R-SPONDIN2Developmental cell · 2022Article
- Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single-Cell Resolution using a Microfluidic Tumor Microenvironment Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BMP signaling plays key roles in development, stem cells, adult tissue homeostasis, and disease. How BMP receptors are extracellularly modulated and in which physiological context, is therefore of prime importance. R-spondins (RSPOs) are a small family of secreted proteins that co-activate WNT signaling and function as potent stem cell effectors and oncogenes. Evidence is mounting that RSPOs act WNT-independently but how and in which physiological processes remains enigmatic. Here we show that RSPO2 and RSPO3 also act as BMP antagonists. RSPO2 is a high affinity ligand for the type I BMP receptor BMPR1A/ALK3, and it engages ZNRF3 to trigger internalization and degradation of BMPR1A. In early Xenopus embryos, Rspo2 is a negative feedback inhibitor in the BMP4 synexpression group and regulates dorsoventral axis formation. We conclude that R-spondins are bifunctional ligands, which activate WNT- and inhibit BMP signaling via ZNRF3, with implications for development and cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.