NEURONAL PATHFINDING BY IDENTIFIED MOTONEURONS

候选人的长期目标是了解神经元的命运是如何 以及神经元如何找到和识别其适当的突触 发展过程中的合作伙伴。当前应用程序的目标是 有两个方面：1)考察环境因素如何引导植物生长 在发育过程中识别细胞特异性靶点的神经元和2) 使应聘者能够学习和实施分子和遗传学 在她的实验室里接近。这些新的方法将补充细胞 目前在候选人实验室中使用的方法，允许她解决 神经发育的现象学和机制。这个 应聘者有幸在俄勒冈大学学院工作 神经科学，在那里她与其他实验室进行日常互动，这些实验室也 研究神经元发育。研究所非常支持她 渴望接受额外的培训，这样她就可以扩大她的研究范围， 她已经得到了减少教学和其他方面的承诺 如果她获得这一奖项，她将承担学业责任。 拟议的研究将在一种简单的脊椎动物身上进行， 胚胎斑马鱼，在那里可以识别单个神经元和它们的 在活体胚胎中直接观察到的发育。候选人提议 检查目标肌肉是否产生促进 所有运动神经元或指示信号的生长锥体的延长 引导特定运动神经元的生长锥作为它们的先驱 通向细胞特定靶点的细胞特定路径。两国之间的关系 已识别的运动神经元及其目标肌肉将由 肌肉前体和运动神经元移植及其后续途径 将观察已识别运动神经元的生长锥体所作的选择。 在活的胚胎中。 候选人建议比较两个人的寻路能力 在不同的时间发育的运动神经元种群，学习 它们的生长锥体是否使用不同的线索来达到相同的目标 肌肉。开创性的运动神经元将使用激光照射来消融 了解追随者是否需要他们的存在才能正确寻路 运动神经元。 候选人建议使用遗传和分子方法来分离 推测的引导分子并研究它们的导向机制 探路，并研究规范的基础机制 神经元的命运。

The candidate's long term goals are to understand how neuronal fate becomes specified and how neurons find and recognize their appropriate synaptic partners during development. The goal of the current application is two-fold: 1) to examine how environmental cues guide the growth cones of identified neurons to cell-specific targets during development and 2) to enable the candidate to learn and implement molecular and genetic approaches in her lab. These new approaches will complement the cellular approach currently used in the candidate's lab by allowing her to address both the phenomenology and the mechanisms of neuronal developmental. The candidate is fortunate to work in the University of Oregon Institute of Neuroscience, where she has daily interactions with other labs that also investigate neuronal development. The Institute is very supportive of her desire to receive additional training so that she can broaden her research, and she has received a commitment for a reduction in teaching and other academic responsibilities if she receives this award. The proposed studies will be carried out in a simple vertebrate, the embryonic zebrafish, where individual neurons can be identified and their development observed directly in living embryos. The candidate proposes to examine whether target muscles produce permissive signals that promote elongation of the growth cones of all motoneurons or instructive signals that guide the growth cones of particular motoneurons as they pioneer cell-specific pathways to cell-specific targets. The relationship between identified motoneurons and their target muscles will be altered by transplanting muscle precursors and motoneurons, and the subsequent pathway choices made by the growth cones of identified motoneurons will be observed in living embryos. The candidate proposes to compare the pathfinding abilities of two populations of motoneurons that develop at different times, to learn whether their growth cones use different cues to reach the same target muscle. Pioneering motoneurons will be ablated using laser-irradiation to learn whether their presence is required for proper pathfinding by follower motoneurons. The candidate proposes to use genetic and molecular approaches to isolate putative guidance molecules and study the mechanisms by which they direct pathfinding, and to study the mechanisms underlying the specification of neuronal fate.