GUIDANCE OF MOTONEURON GROWTH CONES

神经元和靶点之间的精确联系是如何发展起来的？ 一个简单的脊椎动物系统的实验和描述性研究， 雏鸡胚胎肌肉神经的发育 研究表明，通过个体的成长进行选择性寻路 神经突起(“生长锥体”)在 所需的精确和有序连接的起源 对于神经系统的功能。到目前为止，人们对此知之甚少。 生长锥体导向的细胞和分子机制。这个 拟议的研究有助于解决这一重大问题 神经生物学中尚未解决的问题。 建议的研究的中心目标是分析时间上的 和导航提示的空间分布，并对其进行表征 在单个生长锥体水平上的指导。特异神经元 用一种无毒荧光染料标记种群 通过图像增强实现活动生长锥体的可视化 技术中央研究分析了 个体生长锥体内生长时带有导航提示 培养中的雏鸡胚胎的活体部分。这种文化 范式在很大程度上保留了萌芽环境，但允许 更大空间度的生长锥体导航分析 和时间分辨率比到目前为止都是可能的。 第一个特定目标的研究涉及轴向导航 运动神经元。众所周知，这些运动神经元需要很长的- 距离外轴肌的距离，以便长出来。这个 拟议的研究将表征生长锥体如何对 提示，确定时空分布、来源和 球杆的有效寿命，表明体细胞是否是必需的 为了使生长锥体对提示做出反应，阐明了 活跃生长锥体的内部结构和轴突如何选择 两个可能的轴外肌靶点之一。在美国的研究 第二个特定目标是解决与轴突通路交界处的三个组织 并且似乎通过充当轴突的屏障来引导轴突生长 进步。拟议的研究将绘制时间-空间图 屏障功能的发展，分子的探针 定义这一功能并确定细胞机制 指导。第三个具体目标是获得单锥抗体。 靶向派生的外轴线索、屏障组织或 运动神经元的亚群。拟议中的研究可能会 提供关于细胞和分子的挑衅性信息 轴突引导线索的性质。 分析细胞和分子机制是 有效的是在雏鸡中特定的神经元寻路应该给予 对人类神经正常和异常发育的洞察 系统。影响复合型经济发展的重要因素 相互依赖的神经肌肉系统最终可能被操纵 治疗神经-肌肉相互作用的缺陷 对人类疾病的状态负责。最后，和理解 对胚胎发育具有专一性的过程 关系是与理解和适当对待有关的 人类特有的神经再生能力相对较差。

How do precise connections develop between neurons and targets? Experimental and descriptive studies of a simple vertebrate system, the development of muscle innervation in the chick embryo, have shown that selective pathfinding by the growing of individual neurites (the "growth cones") plays an essential role in the genesis of the precise and orderly connections that are required for the nervous system of function. As yet, little is known about the cellular and molecular mechanisms of growth cone guidance. The proposed studies contribute to the resolution of this major unsolved problem in neurobiology. The central aim of the proposed studies is to analyze the temporal and spatial distribution of navigational cues and to characterize guidance at the level of individual growth cones. Specific neural populations are labeled with a non-toxin fluorescent dye that allows visualization of active growth cones with image enhancement technology. The central studies analyze the interactions of individual growth cones with navigational cutes as they grow within living sections of the chick embryo in culture. This culture paradigm largely preserves the embryonic environment and yet allows analysis of growth cone navigation with a greater degree of spatial and temporal resolution than has heretofore been possible. Studies in the first specific aim address the navigation of epaxial motoneurons. These motoneurons are known to require a long- distance cue from the epaxial muscles in order to grow out. The proposed studies will characterize how growth cones respond to the cue, determine the spatial-temporal distribution, source and effective lifetime of the cue, show if the somata are essential for growth cones to respond to the cue elucidate changes in the internal structure of active growth cones and show how axons choose one among two possible epaxial muscle targets. Studies in the second specific aim address three tissues that border axon pathways and appear to channel axon outgrowth by acting as barriers to axon advancement. The proposed studies will chart the temporal-spatial development of the barrier function, probe for molecules that define this function and determine the cellular mechanism of guidance. The third specific aim is to obtain monoconal antibodies to the target-derived epaxial cue, the barrier tissues or to subpopulations of motoneurons. The studies proposed are likely to provide provocative information on the cellular and molecular nature of axonal guidance cues. Analysis of the cellular and molecular mechanisms that are effective is specific neuronal pathfinding in the chick should give insights into normal and abnormal development of the human nervous system. Factors important to the development of the complexly interdependent neuromuscular system may eventually be manipulated to treat deficiencies in nerve-muscle interactions that are responsible for human disease states. Finally, and understanding of the processes conferring specificity on developing embryonic connections is relevant to an understanding and proper treatment of the relatively poor specific nerve regeneration in humans.