R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling

• DOI: 10.1093/hmg/ddn036
• Publication Date: 2008-02-04T20:25:28Z
• Authors: Kazuma Tomizuka; Kaori Horikoshi; Rina Kitada; Yuriko Sugawara; Yumi Iba; Ayako Kojima; Akiko Yoshitome; Kengo Yamawaki; Mikiko Amagai; Ayano Inoue; Takeshi Oshima; Makoto Kakitani
• Keywords: Testis determining factor; WNT4; Gonadal ridge; Sex reversal

In mammals, female development has traditionally been considered a default process in the absence of testis-determining gene, Sry. Recently, it documented that gene for R-spondin1 (RSPO1), novel class soluble activator Wnt/beta-catenin signaling, is mutated two Italian families with female-to-male (XX) sex reversal. To elucidate role Rspo1 as candidate female-determining mouse model, we generated Rspo1-null (Rspo1(-/-)) mice and found Rspo1(-/-) XX displayed masculinized features including pseudohermaphroditism genital ducts, depletion fetal oocytes, male-specific coelomic vessel formation ectopic testosterone production ovaries. Thus, although required to fully suppress male differentiation program maintain germ cell survival during gonads, loss its activity proved be insufficient cause complete reversal mice. Interestingly, these partial sex-reversed phenotypes recapitulated those previously described Wnt-4(-/-) accordance this finding, expression Wnt-4 downstream genes was deregulated early suggesting may participate suppressing pathway Sry maintaining oocyte through positively regulating signaling.