Development of sensory axon pathways in zebrafish

在神经发育过程中，轴突在包含多种引导的环境中延伸 影响它们生长和方向的分子。关于轴突是如何形成的，我们还知之甚少。 生长锥在复杂的体内环境中被引导。我们对特定的轴突很感兴趣 一个神经元的两个轴突分支如何沿着不同的路径被引导到 不同的目标。神经元经常将轴突投射到不止一个靶点，而且几乎对此一无所知。 它们的轴突分支是如何被不同地引导的。我们用斑马鱼脊髓感觉神经元作为模型， 这是一个简单的神经元群体，具有很好的轴突轨迹特征。这些神经元延伸了两个 轴突分支，即中央轴突和外周轴突，表现出截然不同的行为和轨迹。这个 该项目的目标是研究这些轴突沿其特定路径的引导机制。 并阐明引导它们的分子线索的功能。斑马鱼的胚胎是一种极好的 研究体内轴突引导机制的系统，因为我们可以很容易地操纵引导 分子和图像对完整活体胚胎轴突生长锥体动态行为的影响。 我们的具体目标是：1)使用活体成像来表征外周轴突的行为 最初沿与中央轴突垂直的方向延伸并离开脊髓，并研究 已知的两个分子在外周轴突延伸中的作用；2)鉴定和分析 参与感觉轴突导引的新分子的功能；3)鉴定和克隆突变的 来自感觉神经轴突通路有缺陷的突变体的基因。 了解促进和抑制轴突生长的复杂过程，以及 引导轴突到达正确靶点的分子的功能对于理解 神经发育。此外，对这些机制的了解将有助于理解这些情况 损伤后轴突可在其下再生。

During neural development, axons extend through an environment containing a multitude of guidance molecules that influence their growth and direction. There is still relatively little known about how axonal growth cones are guided in the complex in vivo environment. We are interested in the particular axon guidance question of how two axon branches from one neuron are guided along separate pathways to distinct targets. Neurons often project axons to more than one target, and virtually nothing is known about how their axon branches are differentially guided. We use as a model zebrafish spinal sensory neurons, which are a simple neuronal population with well-characterized axon trajectories. These neurons extend two axon branches, the central and peripheral axons, that display very different behaviors and trajectories. The goal of this project is to investigate mechanisms of guidance of these axons along their particular pathways and to elucidate the function of the molecular cues that guide them. The zebrafish embryo is an excellent system to investigate axon guidance mechanisms in vivo because we can readily manipulate guidance molecules and image effects on dynamic behavior of axonal growth cones in the intact living embryo. Our specific aims are: 1) to use live imaging in vivo to characterize the behavior of the peripheral axon as it initially extends in an orthogonal direction to the central axon and exits the spinal cord, and investigate the roles of two molecules known to be important for peripheral axon extension; 2) to identify and analyze the function of new molecules involved in sensory axon guidance; and 3) to characterize and clone the mutated gene from a mutant that has defective sensory axon pathways. An understanding of the complex processes involved in promoting and inhibiting axon growth, and the functions of molecules that guide axons to their correct targets will be crucial for understanding diseases of neural development. Moreover, knowledge of these mechanisms will help to understand the conditions under which axon regeneration after injury can occur.