RSPO1

R-spondin-1 is a secreted protein that in humans is encoded by the Rspo1 gene, found on chromosome 1. In humans, it interacts with is_associated_with::WNT4 in the process of female sex development. Loss of function can cause female to male sex reversal. Furthermore, it promotes canonical WNT/β catenin signaling.

Structure
The protein has two is_associated_with::cysteine-rich, is_associated_with::furin-like domains and one thrombospondin type 1 domain.

Early Gonads
RSPO1 is required for the early development of gonads, regardless of sex. It has been found in mice only eleven days after is_associated_with::fertilization. To induce cell proliferation, it acts synergistically with is_associated_with::WNT4. They help stabilize is_associated_with::β-catenin, which activates downstream targets. If both are deficient in XY mice, there is less expression of is_associated_with::SRY and a reduction in the amount of is_associated_with::SOX9. Moreover, defects in vascularization are found. These occurrences result in testicular is_associated_with::hypoplasia. Male to female sex reversal, however, does not occur because is_associated_with::Leydig cells remain normal. They are maintained by steroidogenic cells, now unrepressed.

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 is_associated_with::fertilization, the ovaries upregulate it while the testes downregulate it.

is_associated_with::Mucositis
is_associated_with::Oral mucosa has been identified as a target tissue for RSPO1. When administered to normal mice, it causes nuclear translocation of is_associated_with::β-catenin to this region. Modulation of the WNT/β catenin pathway occurs through the relief of is_associated_with::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 is_associated_with::mucositis, which is characterized by inflammation of the oral cavity. This unfortunate condition often accompanies is_associated_with::chemotherapy and radiation in cancer patients with head and neck tumors. RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice.