Endothelins and sympathetic innervation of the heart

描述（由申请人提供）：在胚胎发育期间，心脏由控制心率和收缩性的交感神经支配。交感神经沿着沿着血管延伸到达它们的目标，这就是所谓的“神经血管一致性”，但实际上对这些轴突如何被指示到达心脏以建立精确的回路一无所知。本提案中描述的新观察结果导致了一种模型，其中来自特定血管成分的内皮素信号传导是交感神经轴突采取适当路线以到达心脏的关键指导机制。在这个应用中，使用在体内和体外试验，我提出的实验，以解决心脏轴突的指导内皮素信号的特定组件的空间和功能的作用。我在发展的背景下，协调神经元生长与心血管细胞谱系和形态发生的方法。

DESCRIPTION (provided by applicant): During embryonic development, the heart becomes innervated by sympathetic nerves, which control heart rate and contractility. Sympathetic nerve extend along blood vessels to reach their targets, in what is called "neurovascular congruency", but virtually nothing is known of how these axons are instructed to reach the heart in order to establish a precise circuitry. New observations described in this proposal lead to a model in which endothelin signaling from specific vascular components is a critical guidance mechanism for sympathetic axons to take appropriate routes in order to reach the heart. In this application, using both in vivo and in vitro assays, I propose experiments to address the spatial and functional role of specific components of endothelin signaling in cardiac axon guidance. I approach this strategy within a developmental context that coordinates neuronal outgrowth with cardiovascular cell lineage and morphogenesis.