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R-spondins are BMP receptor antagonists in Xenopus early embryonic development.

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.

SUBMITTER: Lee H

PROVIDER: S-EPMC7642414 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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R-spondins are BMP receptor antagonists in Xenopus early embryonic development.

Lee Hyeyoon H Seidl Carina C Sun Rui R Glinka Andrey A Niehrs Christof C

Nature communications 20201104 1

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 R ...[more]

PMID: 33149137

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A Xenopus DNA microarray approach to identify novel direct BMP target genes involved in early embryonic development

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