Development of sensory axon pathways in zebrafish

斑马鱼感觉轴突通路的发育

基本信息

批准号：
7848288
负责人：
MARY C HALLORAN
金额：
$ 30.86万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2012-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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 zebrafish spinal sensory neurons as a model because they are a simple neuronal type with well- characterized simple axon trajectories. These neurons extend two main axon branches, the central and peripheral axons, which 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 mechanism 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, investigate the roles of two molecules known to be important for peripheral axon extension, and investigate the intracellular signaling events underlying the differential axon guidance; 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. Overall, our studies are designed to understand the processes involved in promoting and inhibiting axon growth, and patterning the complex arborization patterns of the nervous system. Knowledge of these mechanisms is important for understanding diseases of neural development and the conditions under which axon regeneration after injury can occur. Project Narrative: An understanding of the complex processes involved in promoting and inhibiting neuronal 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.

描述（由申请人提供）：在神经发育过程中，轴突延伸穿过包含大量影响其生长和方向的引导分子的环境。关于轴突生长锥在复杂的体内环境中如何被引导仍然知之甚少。我们对特定的轴突引导问题感兴趣，即一个神经元的两个轴突分支如何沿着不同的路径引导到不同的目标。神经元经常将轴突投射到多个目标，而实际上对于它们的轴突分支如何被差异化引导一无所知。我们使用斑马鱼脊髓感觉神经元作为模型，因为它们是一种简单的神经元类型，具有特征明确的简单轴突轨迹。这些神经元延伸出两个主要的轴突分支，即中央轴突和外周轴突，它们表现出截然不同的行为和轨迹。该项目的目标是研究这些轴突沿着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。斑马鱼胚胎是研究体内轴突引导机制的绝佳系统，因为我们可以轻松操纵引导分子和图像对完整活体胚胎中轴突生长锥动态行为的影响。我们的具体目标是 1) 使用体内实时成像来表征外周轴突的行为，因为它最初沿与中央轴突正交的方向延伸并退出脊髓，研究已知对外周重要的两种分子的作用轴突延伸，并研究差异轴突引导下的细胞内信号传导事件； 2）识别和分析参与感觉轴突引导的新分子的功能； 3) 表征并克隆来自感觉轴突通路缺陷的突变体的突变基因。总的来说，我们的研究旨在了解促进和抑制轴突生长的过程，以及神经系统复杂的树枝化模式。了解这些机制对于了解神经发育疾病以及损伤后轴突再生的条件非常重要。项目叙述：了解促进和抑制神经元轴突生长的复杂过程，以及引导轴突到达正确目标的分子的功能对于理解神经发育疾病至关重要。此外，了解这些机制将有助于了解损伤后轴突再生发生的条件。