DEVELOPMENT OF NEURONAL SPECIFICITY

一般指导线索定义轴突遵循的共同路径， 负责轴突生长的刻板解剖模式。 胚胎手术已经通过实验确定了三对 组织为感觉和运动神经元提供一般的指导线索， 鸡胚 所有这三对组织都通过提供一个 一条允许轴突前进的“路径”和一条允许轴突前进的“路径”之间的对比， “屏障”是相对抑制性的，具有积极主动的回避作用 胚胎的反应。中心目标是识别细胞 相互作用，介导积极和回避反应的运动和 感觉神经元的每一个这些路径和障碍，并开始开始， 确定一般指导机制是否与其他机制相同， 神经细胞群和神经嵴细胞。 前两个目标将 定义介导运动神经元反应的细胞相互作用， 神经元（AIM 1）和感觉神经元（AIM 2）到每对路径/屏障。 趋化相互作用的贡献和两种不同类型的 接触介导的相互作用将使用灵敏的测定来建立， 文化 接触如何改变丝状伪足活动的分析 将首次详细研究 视锥与细胞的相互作用，在一个 脊椎动物胚胎 这项工作将确定细胞机制 负责感觉和运动发育的每一个寻路选择 圆锥体。 目的3将确定是否其他PNS和CNS神经元可以响应 敏感培养物测定中的代表性路径/屏障对， 因此，将开始确定这些机制在多大程度上 共同 目的4询问真皮是否是两个神经嵴的暂时屏障 细胞和感觉轴突。 免疫细胞化学将显示真皮 瞬时表达已知屏障的典型标志物， 手术将通过实验确定是否存在时间变化， 在真皮中从抑制性变为阳性。 目标5解决另一个问题 时间方面的指导。 胚胎手术将验证这一假设 皮肌刀对于神经嵴细胞迁移到 它们在交感神经节中的腹侧目的地， 腹侧迁移发展。 在这些目标的个别研究将扩大 我们对运动神经元、感觉神经元 和神经嵴细胞。整个提案将阐明 一般指导中的特定人群差异，并将评估 一般指导机制对许多人来说是共同的， 神经元和神经嵴细胞。 确定指导要素 轴突和细胞在发育中的胚胎是相关的治疗 人类神经疾病和损伤后的病变。

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.