RSPO4

RSPO4 encodes R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling.

Rspo4 expression is localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis.

RSPO4 is a member of the recently described R-spondin family of secreted proteins that play a major role in activating the Wnt/ beta -catenin signaling pathway.

Wnt signaling is evolutionarily conserved and plays a pivotal role in embryonic development, growth regulation of multiple tissues, and cancer development.

Mesenchymal-epithelial interactions are crucial in nail development and anonychia is on the growing list of congenital malformation syndromes caused by Wnt-signaling-pathway defects.

Pathology

 RSPO4 germline mutations in inherited anonychia and hyponychia congenita (MIM.206800) (17186469, 17041604)

• Anonychia is an autosomal recessive disorder characterized by the congenital absence of finger- and toe-nails.
• RSPO4 is a member of the recently described R-spondin family of secreted proteins that play a major role in activating the Wnt/ beta -catenin signaling pathway.

References

 Bergmann C, Senderek J, Anhuf D, Thiel CT, Ekici AB, Poblete-Gutierrez P, van Steensel M, Seelow D, Nürnberg G, Schild HH, Nürnberg P, Reis A, Frank J, Zerres K. Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. Am J Hum Genet. 2006 Dec;79(6):1105-9. PMID: 17186469

 Blaydon DC, Ishii Y, O’toole EA, Unsworth HC, Teh MT, Ruschendorf F, Sinclair C, Hopsu-Havu VK, Tidman N, Moss C, Watson R, de Berker D, Wajid M, Christiano AM, Kelsell DP. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. Nat Genet. 2006 Nov;38(11):1245-7. PMID: 17041604