GUIDANCE OF MOTONEURON GROWTH CONES

神经元和目标之间的精确连接是如何发展的？ 简单脊椎动物系统的实验和描述性研究， 鸡胚肌肉神经支配的发育， 显示了通过个体生长选择性寻路 神经突（"生长锥"）在神经生长中起着重要作用。 精确而有序的连接的起源， 神经系统的功能。 到目前为止，人们对 生长锥引导的细胞和分子机制。 的 建议的研究有助于解决这一重大问题， 神经生物学中未解决的问题。 所提出的研究的中心目的是分析时间 和空间分布的导航线索，并表征 在个体生长锥的水平上进行指导。 特定的神经 用无毒荧光染料标记种群， 允许通过图像增强显示活跃的生长锥 技术. 中心研究分析了 当它们在其中生长时， 培养中的鸡胚活切片。 这种文化 范式在很大程度上保留了胚胎环境， 分析增长锥导航与更大程度的空间 和时间分辨率都要高 第一个特定目标的研究涉及轴上导航 运动神经元 众所周知，这些运动神经元需要长时间的- 从轴上肌肉的距离线索，以增长出来。 的 拟议的研究将描述生长锥如何响应 线索，确定时空分布，来源和 线索的有效寿命，显示胞体是否是必需的 对于生长锥响应线索阐明的变化， 活动生长锥的内部结构，并显示轴突如何选择 两个可能的轴上肌肉目标之一 的研究 第二个具体目标是解决三个组织的边界轴突通路 似乎通过充当轴突生长的屏障来引导轴突生长 进步。 拟议的研究将绘制时空图， 屏障功能的发展，探针分子， 定义这种功能，并确定细胞机制， 指导 第三个具体目标是获得单克隆抗体 靶源性轴上线索、屏障组织或 运动神经元的亚群。 拟议的研究可能会 提供了关于细胞和分子 轴突引导线索的性质。 分析细胞和分子机制， 有效的是特定的神经元寻路在小鸡应该给 对人类神经系统正常和异常发育的洞察 系统 发展的重要因素复杂 相互依赖的神经肌肉系统最终可能被操纵 来治疗神经肌肉相互作用的缺陷， 负责人类疾病状态。 最后，理解 赋予胚胎发育特异性的过程 联系与理解和适当治疗相关 人类相对较差的特定神经再生。

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.