Beta -catenin in testicular development and tumorigenesis

Hao Chang, The University of Texas Grad. Sch. of Biomed. Sci. at Houston


β-catenin, as an important effector of the canonical Wnt signaling pathway and as a regulator of cell adhesion, has been demonstrated to be involved in multiple developmental processes and tumorigenesis. However, its potential role in Sertoli cells during testis formation and testicular tumorigenesis has not been examined. To determine the function of β-catenin in Sertoli cells during testis formation, we either deleted β-catenin or expressed a constitutively active form of β-catenin in Sertoli cells. We found that deletion of β-catenin in Sertoli cells caused no detectable abnormalities. However, stabilization of β-catenin in Sertoli cells caused severe phenotypes, including testicular cord disruption, germ cell depletion and inhibition of Müllerian duct regression. β-catenin stabilization in Sertoli cells caused changes in Sertoli cell identity, including loss of the male marker Sox9 and ectopic expression of the female marker Wnt4. Sertoli cell knockout of Sox9 did not lead to testis abnormalities, suggesting that the loss of Sox9 only was not sufficient to cause the phenotypes in stabilized β-catenin mutants. In older mice, the testicular lesions in stabilized β-catenin mutants often evolved into Sertoli cell tumors. Together, we found that Sertoli cell expression of β-catenin is not essential for testis formation, while the stabilization of β-catenin in Sertoli cells causes the disruption of testicular cords and eventually causes Sertoli cell tumors. These studies show a causal link between misregulated β-catenin signaling and Sertoli cell tumor development and provide a novel model for the future study of Sertoli cell tumor biology. In this dissertation, we also generated a Sox9 conditionally overexpressing allele that will be a very useful tool to study gonad development and tumorigenesis. ^

Subject Area

Biology, Genetics|Health Sciences, Oncology

Recommended Citation

Chang, Hao, "Beta -catenin in testicular development and tumorigenesis" (2008). Texas Medical Center Dissertations (via ProQuest). AAI3339605.