Genes Essential To Motor Axon Guidance in Drosophila

描述(由申请人提供)：在神经系统发育和再生过程中，需要控制生长锥导航到适当目标细胞的细胞内机制来建立功能神经连接网络。我们对多个导向受体下游的细胞骨架信号机制的长期兴趣使我们发现了一系列保守的微管相关蛋白，它们似乎介导了不同类型的导向行为。对效应器蛋白CLAP的分析已经确定了一条从排斥因子Sit及其转折受体到Abelson酪氨酸激酶再到CLAP的途径，作为阻止微管和前沿推进的一种手段。Abl如何协调微丝和微管的动力学，以及控制CLAP或其相关伙伴的活动尚不清楚。初步数据表明，几个直接或间接与CLAP相关的蛋白质是准确的中线排斥所必需的，而其他微管效应蛋白似乎在早期轴突指导决策中扮演着不同的角色。我们将结合遗传学、细胞生物学和生物化学来确定每种蛋白质在轴突引导下的功能，并剖析调节关键效应器活动的信号机制。

DESCRIPTION (provided by applicant): The intracellular mechanisms that control growth cone navigation to appropriate target cells are required to build networks of functional neural connections during nervous system development and regeneration. Our long-standing interest in the cytoskeletal signaling machinery downstream of multiple guidance receptors has led us to a series of conserved microtubule-associated proteins that appear to mediate different types of guidance behavior. Analysis of the effector protein CLASP has defined a pathway from the repellent factor Slit and its Roundabout receptors, to the Abelson tyrosine kinase, to CLASP, as a means of impeding microtubule and leading edge advance. How Abl acts to coordinate microfilament and microtubule dynamics, and control the activity of CLASP or its associated partners is unknown. Preliminary data indicates that several proteins directly or indirectly linked to CLASP are required for accurate midline repulsion, whereas other microtubule effector proteins appear to play distinct roles in early axon guidance decisions. We will use a combination of genetics, cell biology and biochemistry to determine each protein's function in axon guidance and to dissect the signaling mechanisms that regulate the key effector activities.