GUIDANCE OF MOTONEURON GROWTH CONES

运动神经元生长锥的引导

• 批准号: 3413977
• 负责人: KATHRYN W TOSNEY
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413977
• 关键词: axon; biological information processing; chick embryo; chickens; cytoskeleton; electron microscopy; fluorescent dye /probe; growth cones; histology; image enhancement; innervation; laboratory mouse; monoclonal antibody; motor neurons; tissue /cell culture

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.

神经元和靶标之间如何发展精确的连接？ 简单脊椎动物系统的实验和描述性研究， 雏鸡胚胎中肌肉神经的发展具有 表明个人成长的选择性探索 神经突（“生长锥”）在 所需的精确和有序连接的起源 用于神经功能系统。 到目前为止，还鲜为人知 生长锥引导的细胞和分子机制。 这 拟议的研究有助于解决这一主要的研究 神经生物学中未解决的问题。 拟议研究的核心目的是分析时间 和导航提示的空间分布并表征 在个体生长锥水平的指导。 具体神经 种群用非毒素荧光染料标记 允许使用图像增强的活性生长锥可视化 技术。 中央研究分析了 带有导航切割时的个体生长锥，它们在内部生长 雏鸡胚胎在文化中的生存部分。 这种文化 范式在很大程度上保留了胚胎环境，但允许 分析生长锥导航的空间更大程度 和时间分辨率比迄今为止的可能性是可能的。 第一个特定目的的研究解决了epaxial的导航 运动神经元。 这些运动神经元已知需要长期 距离肌肉的距离提示为了长大。 这 拟议的研究将表征生长锥如何应对 提示，确定时空分布，来源和 提示的有效寿命，显示somata是否必不可少 生长锥以响应提示的阐明 主动生长锥的内部结构并显示轴突如何选择 一个可能的肾上腺肌靶标之一。 研究 第二个特定目的解决边界轴突途径的三个组织 并通过充当轴突的障碍来引导轴突的生长 进步。 拟议的研究将绘制时间空间 屏障功能的发展，对分子的探测 定义此功能并确定 指导。 第三个具体目的是获得单骨抗体 到目标衍生的层状提示，屏障组织或 运动神经元的亚群。 提出的研究可能是 提供有关细胞和分子的挑衅性信息 轴突指导的性质。 分析细胞和分子机制 有效的是小鸡中的特定神经元探测 洞悉人类神经正常和异常发育 系统。 对复杂发展重要的因素 相互依存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 负责人类疾病状态。 最后，理解 赋予开发胚胎的特异性的过程 联系与理解和适当的治疗有关 人类相对较差的特异性神经再生