R-spondin-1
Developmental stage
Transiently expressed in the central nervous system (CNS) during development. Predominantly expressed in the tailbud of embryos. Also detected in the primitive streak, dorsal neural tube, forebrain and migrating neural crests of embryos. Detected from day 9.5, in various neural and mesodermal derivatives, mainly along dorsal neural tube and diencephalon. Strongly expressed in limb buds, particularly in the morphogenetically active region such as the apical ectodermal ridge (AER). The developing skin showed expression in patches of the developing dermis at 12.5 dpc and at lower levels at 14.5 dpc. By 18.5 dpc expression is restricted to the dermal papilla of the developing hair, which persisted into adulthood. In the developing kidney, strong expression at 11.5 dpc in the uninduced metanephric mesenchyme is observed. By 14.5 dpc this expression is restricted to the condensing mesenchyme surrounding the ureter and the developing nephrons. Specific expression in the urogenital ridge as early as 10.5 dpc in the coelomic epithelium. Sex-specific differences of expression began to appear starting at 12.5 dpc, with an increase in the somatic cells of the XX gonad.
Domain
The FU repeats are required for activation and stabilization of beta-catenin.
Function
Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes (PubMed:21693646). Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination (By similarity). Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (By similarity).
Post-translational modifications
C-, and N-glycosylated. N-glycosylation at Asn-137, negatively influences its secretion and enhancing effect on Wnt/beta-catenin signaling. C-mannosylation at Trp-156 by DPY19L3 is required for its secretion an regulates the enhancing activity of Wnt signaling.
Sequence Similarities
Belongs to the R-spondin family.
Tissue Specificity
Expressed in the dorsal part of the neural tube on 10 and 12 dpc, especially in the boundary region between roof plate and neuroepithelium. This expression is enhanced in the rostral part. Also expressed in other tissues such as truncal region neighboring forelimbs and mesenchymal tissues around the nasal cavity.
Cellular localization
- Secreted
- Nucleus
- Seems to mainly localize to nucleoli.
Alternative names
R-spondin-1, Cysteine-rich and single thrombospondin domain-containing protein 3, Roof plate-specific spondin-1, Cristin-3, mCristin-3, Rspo1