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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 |

REPOSITORIES: biostudies-literature

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Role of TAK1 and TAB1 in BMP signaling in early Xenopus development.

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Project description:Bone Morphogenetic Proteins (BMPs), a subgroup of the TGF-beta superfamily, were originally isolated from bone on the basis of their ability to induce ectopic bone development. While BMPs are involved in a wide range of developmental and physiological functions, very few vertebrate target genes in this pathway have been identified. To identify target genes regulated by the BMP growth factor family in Xenopus, large-scale microarray analyses were conducted to discover genes directly activated by this factor in dissociated animal cap tissues treated with a combination of the protein synthesis inhibitor cycloheximide and BMP2. Keywords = Xenopus Keywords = BMP Keywords = microarray Keywords = development Keywords = target genes Keywords: parallel sample

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Project description:In ectodermal explants from Xenopus embryos, inhibition of BMP signaling is sufficient for neural induction, leading to the idea that neural fate is the default state in the ectoderm. Many of these experiments assayed the action of BMP antagonists on animal caps, which are relatively naïve explants of prospective ectoderm, and different results have led to debate regarding both the mechanism of neural induction and the appropriateness of animal caps as an assay system. Here we address whether BMP antagonists are only able to induce neural fates in pre-patterned explants, and the extent to which neural induction requires FGF signaling. We suggest that some discrepancies in conclusion depend on the interpretations of sox gene expression, which we show not only marks definitive neural tissue, but also tissue that is not yet committed to neural fates. Part of the early sox2 domain requires FGF signaling, but in the absence of organizer signaling, this domain reverts to epidermal fates. We also reinforce the evidence that ectodermal explants are naïve, and that explants that lack any dorsal prepattern are readily neuralized by BMP antagonists, even when FGF signaling is inhibited.

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

Project description:Bone Morphogenetic Proteins (BMPs), a subgroup of the TGF-ï¢ superfamily, were originally isolated from bone on the basis of their ability to induce ectopic bone development. While BMPs are involved in a wide range of developmental and physiological functions, very few vertebrate target genes in this pathway have been identified. To identify target genes regulated by the BMP growth factor family in Xenopus, large-scale microarray analyses were conducted to discover genes directly activated by this factor in dissociated animal cap tissues treated with a combination of the protein synthesis inhibitor cycloheximide and BMP2. Keywords = Xenopus Keywords = BMP Keywords = microarray Keywords = development Keywords = target genes

2010-06-10 | E-GEOD-2274 | biostudies-arrayexpress

The E3 ubiquitin ligase Hace1 is required for early embryonic development in Xenopus laevis.

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RMND5 from Xenopus laevis is an E3 ubiquitin-ligase and functions in early embryonic forebrain development.

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