DEVELOPMENT OF NEURONAL SPECIFICITY

一般引导线索定义轴突遵循的公共路径 对轴突生长的刻板解剖模式负责。 胚胎手术已经实验证实，有三对 组织为大脑中的感觉和运动神经元提供一般的指导线索。 小鸡胚胎。这三对组织都通过提供一种 允许轴突前进的“路径”与允许轴突前进的 相对抑制并引起主动回避的“障碍” 胚胎中的反应。中心目标是识别细胞 调节运动和回避反应的相互作用 感觉神经元连接到这些路径和障碍中的每一个，并开始 确定一般指导机制是否适用于其他 神经群体和神经脊细胞。前两个目标将 定义调节马达反应的细胞相互作用 神经元(目标1)和感觉神经元(目标2)连接到每对路径/障碍。 趋化相互作用的贡献和两类不同的 将使用灵敏的分析建立接触中介的交互作用 文化。接触对丝径活动影响的分析 与路径和屏障细胞将提供第一个详细的生长研究 与在中定义了指导角色的单元格的锥体交互 脊椎动物胚胎。这项工作将确定细胞机制 负责感官和运动成长的每一次寻路选择 圆锥体。目标3将确定其他三叉神经节和中枢神经系统神经元是否可以做出反应 敏感培养试验中的一对代表性路径/屏障以及 从而开始定义这些机制在多大程度上 很普通。目标4问真皮是否是两个神经峰的暂时性障碍 细胞和感觉神经轴突。免疫细胞化学将显示真皮是否 瞬时表达已知障碍的典型标记，并处于萌芽状态 手术将通过实验确定是否存在时间变化 在真皮中，从抑制性质到积极性质。AIM 5解决了另一个问题 制导的时间方面。胚胎手术将检验这一假设 皮肌节是神经脊细胞迁移到 它们的腹侧目的地在交感神经节障碍之前 腹向迁移发展起来。在这些目标方面的个人研究将延长 我们对引导运动神经元、感觉神经元的机制的理解 和神经脊细胞。整个提案将阐明 在一般指导中针对具体人群的差异，并将评估 一般指导的机制对许多人来说是共同的可能性 神经元和神经脊细胞。确定指导原则的要素 发育中胚胎中的轴突和细胞与糖尿病的治疗有关 人类神经疾病和继发性损伤中的损伤。

General guidance cues define the common pathways that axons follow and are responsible for the stereotyped anatomical patterns of axon outgrowth. Embryonic surgeries have established experimentally that three pairs of tissues provide general guidance cues for sensory and motor neurons in the chick embryo. All three pairs of tissues guide axons by providing a contrast between a "path" that is permissive for axon advance and a "barrier" that is relatively inhibitory and elicits active avoidance responses in the embryo. The central aims are to identify the cellular interactions that mediate the positive and avoidance responses of motor and sensory neurons to each of these paths and barriers and to begin to determine whether the mechanisms of general guidance are common to other neural populations and to neural crest cells. The first two aims will define the cellular interactions that mediate the responses of motor neurons (aim 1) and sensory neurons (aim 2) to each pair of paths/barriers. The contributions of chemotactic interactions and two different classes of contact-mediated interactions will be established using sensitive assays in culture. An analysis of how filopodial activities are altered by contact with path and barrier cells will provide the first detailed study of growth cone interactions with cells that have defined guidance roles in a vertebrate embryo. This work will identify the cellular mechanisms responsible for each of the pathfinding choices of sensory and motor growth cones. Aim 3 will establish whether other PNS and CNS neurons can respond to a representative pair of paths/barriers in a sensitive culture assay and will thereby begin to define the extent to which these mechanisms are common. Aim 4 asks if dermis is a transient barrier for both neural crest cells and sensory axons. Immunocytochemistry will show whether dermis transiently expresses markers typical of the known barriers, and embryonic surgeries will establish experimentally whether there is a temporal change in dermis from inhibitory to positive qualities. Aim 5 addresses another temporal aspect of guidance. Embryonic surgeries will test the hypothesis that the dermamyotome is essential for neural crest cells to migrate to their ventral destination in the sympathetic ganglion before barriers to ventral migration develop. Individual studies in these aims will extend our understanding of mechanisms that guide motor neurons, sensory neurons and neural crest cells. The proposal as a whole will elucidate population-specific differences in general guidance, and will evaluate the possibility that the mechanisms of general guidance are common to many neurons and to neural crest cells. Identification of elements that guide axons and cells in the developing embryo is relevant to the treatment of lesions in human neural diseases and following injury.