Sry is the Y-linked male sex-determining gene. Testis organogenesis is initiated immediately after Sry is expressed. If Sry is not expressed, development of the ovary is initiated ~3 days later from the same bipotential gonadal cell population. If Sry is expressed, the gonad grows dramatically in size and cells rapidly reorganize into cord-like structures; in the absence of Sry expression, little change in size or cellular organization is apparent. Thus Sry is somehow acting to trigger mechanisms that lead to the divergence of organ architecture. Because of the dimorphic male and female pathways, this system provides a rare opportunity to identify molecular and cellular pathways linking the expression of a pivotal gene in development with morphogenetic mechanisms that operate to pattern the development of an organ and the differentiation of its cells.
Our assays have revealed that Sry initiates multiple signaling pathways including those that direct cell migration, cell-cell organization, and proliferation required for morphogenetic divergence along the male pathway. Many approaches are used to characterize differences between male and female gonads including PCR, RNA in situ hybridization, and immunohistochemistry. Genetic and biochemical approaches as well as novel in vivo and organ culture methods are used to identify the signals that control these processes and to experimentally determine their role during organogenesis of the testis.
Current Projects: We will be testing signaling pathways that operate between the sex determination switch gene, Sry, and organogenesis of the testis. Specific projects include work on vascularization, proliferation, migration pathways, and cell fate determination.
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