R-spondin-1 is a secreted protein that in humans is encoded by the RSPO1 gene, found on chromosome 1.[5] In humans, it interacts with
WNT4 in the process of female sex development. Loss of function can cause female to male sex reversal.[6] Furthermore, it promotes canonical
WNT/β catenin signaling.[7]
RSPO1 is required for the early development of gonads, regardless of sex. It has been found in mice only eleven days after
fertilization.[6] To induce cell proliferation, it acts synergistically with
WNT4.[6] They help stabilize
β-catenin, which activates downstream targets. If both are deficient in XY mice, there is less expression of SRY and a reduction in the amount of
SOX9. Moreover, defects in vascularization are found. These occurrences result in testicular
hypoplasia. Male to female sex reversal, however, does not occur because
Leydig cells remain normal. They are maintained by steroidogenic cells, now unrepressed.[6]
Ovaries
RSPO1 is necessary in female sex development. It augments the
WNT/β catenin pathway to oppose male sex development. In critical gonadal stages, between six and nine weeks after
fertilization, the ovaries upregulate it while the testes downregulate it.[8]
Oral mucosa has been identified as a target tissue for RSPO1. When administered to normal mice, it causes nuclear translocation of
β-catenin to this region.[7] Modulation of the
WNT/β catenin pathway occurs through the relief of
Dkk1 inhibition. This occurrence results in increased basal cellularity, thickened mucosa, and elevated epithelial cell proliferation in the tongue. RSPO1 can therefore potentially aid in the treatment of
mucositis, which is characterized by inflammation of the oral cavity. This unfortunate condition often accompanies
chemotherapy and
radiation in cancer patients with head and neck tumors.[7] RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice.[5]
Kamata T, Katsube K, Michikawa M, et al. (2004). "R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants". Biochim. Biophys. Acta. 1676 (1): 51–62.
doi:
10.1016/j.bbaexp.2003.10.009.
PMID14732490.
Parma P, Radi O, Vidal V, et al. (2007). "R-spondin1 is essential in sex determination, skin differentiation and malignancy". Nat. Genet. 38 (11): 1304–9.
doi:
10.1038/ng1907.
PMID17041600.
S2CID9687808.