ORGAN SPECIFIC MECHANISMS OF VASCULAR DEVELOPMENT

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We have designed a novel system in which we can identify and study the signaling events and morphological changes that control the development of specialized vasculature in organs. The bi-potential development of the gonad provides a unique model system. The primitive vasculature in the gonad is identical between males and females until activation of the Y-linked sex-determining gene. Sry, initiates the morphological divergence of testis development. Our novel organ culture system reveals that during and following the window of Sry activity, endothelial and smooth muscle cells are recruited into the XY gonad from the attached mesonephros, whereas, no vascular migration occurs into the XX gonad. The divergence of vascular developmental pathways in the gonad provides a system in which comparative approaches can be used to identify structural specializations of the vasculature between XX and XY gonads and link them to signaling differences that arise that Sry expression. We will test the following hypotheses: . There are different mechanisms shaping vascular development in the gonad. These result in ovary or testis-specific structural specializations of the vasculature. . There are early functional requirements in the male embryo (e.g. hormone expert) that are reflected in specializations of the testing vasculature. . Sry activates male-specific signaling factors that control vascular specifications. By comparing expression patterns during X and XY gonads directly after SRY initiates the male pathway, we have identified several candidate signaling molecules that show activation differences between XX and XY gonads. Our organ culture system provides a direct means to test the effect of candidate factors on cell migration and vascular development. This work will yield important information about the signaling basis of heterogeneity in the formation and structure of ovary versus testis vasculature. Moreover, it serves as a general model of how the development of diverse vascular phenotypes is signaled and integrated with organogenesis throughout the embryo.