ctnnb1 signaling in sertoli cells downregulates spermatogonial stem cell activity via wnt4ctnnb1塞尔托利氏细胞信号会使精原干细胞通过wnt4活动.pdfVIP

CTNNB1 Signaling in Sertoli Cells Downregulates Spermatogonial Stem Cell Activity via WNT4 1 2 2 ` 3 1 Alexandre Boyer , Jonathan R. Yeh , Xiangfan Zhang , Marilene Paquet , Aurore Gaudin , Makoto C. 2 1 Nagano , Derek Boerboom * ´ ´ ´ ´ ´ ´ ´ 1 Animal Reproduction Research Centre (CRRA), Faculte de Medecine Veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada, 2 Department of Obstetrics and ´ ´ ´ ´ Gynecology, McGill University, Montreal, Quebec, Canada, 3 Comparative Medicine and Animal Resources Centre, McGill University, Montreal, Quebec, Canada Abstract Constitutive activation of the WNT signaling effector CTNNB1 (b-catenin) in the Sertoli cells of the Ctnnb1tm1Mmt/+; Amhr2tm3(cre)Bhr/+ mouse model results in progressive germ cell loss and sterility. In this study, we sought to determine if this phenotype could be due to a loss of spermatogonial stem cell (SSC) activity. Reciprocal SSC transplants between Ctnnb1tm1Mmt/+;Amhr2tm3(cre)Bhr/+ and wild-type mice showed that SSC activity is lost in Ctnnb1tm1Mmt/+;Amhr2tm3(cre)Bhr/+ testes over time, whereas the mutant testes could not support colonization by wild-type SSCs. Microarray analyses performed on cultured Sertoli cells showed that CTNNB1 induces the expression of genes associated with the female sex determination pathway, which was also found to occur in Ctnnb1tm1Mmt/+;Amh