Endothelins and sympathetic innervation of the heart

描述(申请人提供)：在胚胎发育期间，心脏受到交感神经的支配，交感神经控制心率和收缩能力。交感神经沿着血管延伸，到达它们的目标，这就是所谓的“神经血管一致性”，但对于这些轴突是如何被指示到达心脏以建立精确的回路，几乎一无所知。这项建议中描述的新观察结果导致了一个模型，在该模型中，来自特定血管组件的内皮素信号是交感神经轴突采取适当路线到达心脏的关键指导机制。在这一应用中，使用体内和体外测试，我建议进行实验，以解决特定成分的内皮素信号在心脏轴突引导中的空间和功能作用。我在一个协调神经元生长与心血管细胞谱系和形态发生的发育背景下探讨这一策略。

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.