ORGAN SPECIFIC MECHANISMS OF VASCULAR DEVELOPMENT

我们设计了一个新的系统，在这个系统中，我们可以识别和研究控制器官中特殊血管发育的信号事件和形态变化。性腺的双潜能发育提供了一个独特的模型系统。在Y连接的性别决定基因被激活之前，性腺中的原始血管系统在男性和女性之间是相同的。SRY启动了睾丸发育的形态分化。我们新的器官培养系统显示，在Sry活动窗口期间和之后，内皮细胞和平滑肌细胞从附着的中肾被招募到XY性腺，而没有血管迁移到XX性腺。性腺中血管发育途径的差异提供了一个系统，在该系统中，可以使用比较方法来识别XX和XY性腺之间的血管结构特化，并将它们与引起Sry表达的信号差异联系起来。我们将检验以下假设：性腺中的血管发育有不同的机制。这些结果导致了卵巢或睾丸特有的维管系统结构特化。。男性胚胎(例如激素专家)的早期功能需求反映在测试血管系统的专门化中。。SRY激活男性特有的信号因子，控制血管规格。通过比较SRY启动雄性通路后X和XY性腺的表达模式，我们已经确定了几个候选信号分子，它们显示了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素对细胞迁移和血管发育的影响。这项工作将提供关于卵巢和睾丸血管形成和结构异质性的信号基础的重要信息。此外，它还作为一个通用模型，说明不同血管表型的发育是如何在整个胚胎中与器官发生相结合的。

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.