P1-SPATIAL REGULATION OF PROTEIN KINASE A SIGNALING DURING GROWTH CONE GUIDANCE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在胚胎发育过程中，神经细胞（或神经元）必须从它们的起源点延伸到适当的目标，以形成神经系统的复杂，相互连接的网络。为了实现这一点，神经元发出长的，电缆状的突起，称为轴突。在生长轴突的顶端是一个能动的感觉结构，称为生长锥。生长锥负责解释它们的细胞外环境，以确定它们是否有更好或更坏的方向延伸。生长锥对靶细胞的适当吸引和远离非靶细胞的排斥对于正确的神经系统发育至关重要。该项目的重点是了解控制神经生长锥响应netrin-1的形状和运动的分子信号通路，netrin-1是在中枢神经系统发育过程中引导轴突的第一个也是最重要的线索之一。我们的工作将定义netrin-1的细胞受体和控制生长锥运动的机制的相互作用，从而深入了解轴突导向和神经发育的分子机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During embryonic development, nerve cells (or neurons) must stretch from their point of origin to reach their proper target in order to form the intricate, interconnected network of the nervous system. To accomplish this, neurons send out long, cable-like projections called axons. At the tip of growing axons is a motile, sensory structure called a growth cone. Growth cones are responsible for interpreting their extracellular environment to determine whether there is a better or worse direction for them to extend. Proper attraction of growth cones towards target cells and repulsion away from off-target cells is fundamentally important for correct nervous system development. This project is focused on understanding the molecular signaling pathways that control the shape and movement of neuronal growth cones in response to netrin-1, the first and one of the most important cues that guide axons during development of the central nervous system. Our work will define the interactions the cellular receptor for netrin-1 and the machinery that controls growth cone movement, and thus lend insight into the molecular mechanisms underlying axon guidance and neural development.