In this new application, the applicant proposes to examine events leading to testis development. The working hypothesis is that testicular development starts immediately after the expression of the Sry gene. Therefore, Sry initiates multiple signaling pathways including those related to direct cell migration, cell-cell interaction and proliferation required for the divergence of the indifferent gonad into testicular organogenesis. Studies include the use of novel in vivo and organ culture methods to define differences in patterns of cell proliferation and migration downstream Sry expression. Two major specific aims are proposed.
Specific Aim 1 will examine cell types contributed by proliferation and migration and the importance of these mechanisms to the development of testis cords in male gonads.
Specific Aim 2 will examine candidate signaling molecules required for the migratory and differentiating cells. The effect of these molecules will be examined by assaying for differential activation between male and female responsive cells, their ability to induce male-specific patterns in a female gonad in culture, and by blocking specific responses in culture assays to test the effects on migration, proliferation or cord formation in male gonads. Null mutants that fail to express specific factors and receptors will be examined to determine phenotypic consequences of genetic interference with migratory or proliferation signals.
