ORGAN SPECIFIC MECHANISMS OF VASCULAR DEVELOPMENT

我们设计了一个新的系统，在其中我们可以识别和研究控制器官中专门脉管系统发育的信号事件和形态学变化。性腺的双电位发育提供了一个独特的模型系统。性腺中的原始脉管系统在男性和女性之间是相同的，直到Y连锁性别决定基因的激活。Sry启动了精巢发育的形态分化。我们的新的器官培养系统表明，在Sry活性窗口期间和之后，内皮细胞和平滑肌细胞从附着的中肾被招募到XY性腺中，而没有血管迁移到XX性腺中。性腺中血管发育途径的分歧提供了一个系统，其中比较方法可用于鉴定XX和XY性腺之间的脉管系统的结构特化，并将它们与引起Sry表达的信号传导差异联系起来。我们将测试以下假设：性腺中的血管发育有不同的机制。这些导致卵巢或睾丸特定的脉管系统结构特化。.男性胚胎的早期功能要求（例如激素专家）反映在测试脉管系统的专业化中。. Sry激活控制血管规格的男性特异性信号因子。通过比较表达模式在X和XY性腺直接SRY启动雄性途径后，我们已经确定了几个候选信号分子，显示XX和XY性腺之间的激活差异。我们的器官培养系统提供了一种直接的手段来测试候选因子对细胞迁移和血管发育的影响。这项工作将产生重要的信息的信号基础的异质性的形成和结构的卵巢与睾丸血管。此外，它作为一个通用的模型，不同的血管表型的发展是如何发出信号，并与整个胚胎器官发生整合。

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.