Thursday 22 December 2005
Wnt-4 is a member of the Wnt family (WNTs) of locally acting secreted growth factors.
Wnt-4 is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups.
Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans.
In testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry.
WNT4 germline mutations in mullerian agenesis (Rokitansky-Kuster-Hauser syndrome)
XY sex reversal associated with a 1p31-p35 duplication including WNT-4.
- Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype.
- WNT-4 and DAX1 play a concerted role in both the control of female development and the prevention of testes formation.
- The mammalian sex determination is sensitive to dosage.
Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Jordan BK, Mohammed M, Ching ST, Délot E, Chen XN, Dewing P, Swain A, Rao PN, Elejalde BR, Vilain E. Am J Hum Genet. 2001 May;68(5):1102-9. PMID: #11283799# (Free)