SENSORY AXON PATHFINDING

感觉轴突寻路

• 批准号: 6393735
• 负责人: Marcia G Honig
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-15 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393735
• 关键词: afferent nerve; blocking antibody; cell adhesion molecules; cell cell interaction; chick embryo; confocal scanning microscopy; developmental neurobiology; immunologic assay /test; motor neurons; neuronal guidance; sensorimotor system; tissue /cell culture

DESCRIPTION (Verbatim from the Applicant's Abstract): The long-range goal of this research is to understand how axons choose the correct pathways to grow along during development. Appropriate pathfinding is crucial for the developing individual because if axons do not find their correct targets, they will not establish the appropriate synaptic connections and the nervous system will not function properly. This research focuses on sensory neurons innervating the chick hindlimb because using such an easily accessible system greatly facilitates experimental manipulations at virtually any point during embryonic development. Previous experiments have shown that, as sensory axons grow into the limb, they respond differentially to cues in the surrounding environment and to other axons, associating with some and separating from others. Preferential adhesivity, mediated by cell adhesion molecules (CAMs), contributes to the ability of sensory axons to fasciculate along appropriate axons and form nerve-specific bundles as they grow distally. The proposed studies will extend previous work examining the roles of fasciculation, CAMs, and environmental cues in sensory axon pathfinding. Retrograde labeling, antibody staining to distinguish between sensory and motoneuron (MN) axons, and confocal microscopy will be combined to examine the trajectories of specific subtypes of sensory axons and their spatial relationships with other axons in a variety of experimental situations. Specifically, some of the proposed studies will use injections of function-blocking antibodies to determine how several CAMs (G4/L1, N-cadherin, DM-GRASP/SC1, axonin-1, NrCAM, neurofascin, and F11) affect sensory/MN axon intermixing, fasciculation, the formation of nerve-specific bundles, and pathfinding by both cutaneous and muscle sensory axons. EM will be used to determine whether sensory axons fasciculate at early stages and after CAM perturbations. Other studies determine whether certain specific limb-associated cues are required for the correct sorting of sensory axons normally destined to project along different peripheral nerves. An important implication of previous findings was that sensory neurons projecting along different peripheral nerves must be different from one another at early stages, as their axons first extend toward the limb. Accordingly, some of the proposed studies will examine differences in gene expression among the different types of sensory neurons.

描述（逐字摘自申请人摘要）：长期目标 这项研究是为了了解轴突如何选择正确的生长路径 在开发过程中一起。正确的路径选择对于发展至关重要 个别的，因为如果轴突没有找到正确的目标，它们就不会 建立适当的突触连接，神经系统不会 功能正常。这项研究的重点是支配感觉神经元 小鸡后肢因为使用如此易于访问的系统大大 促进胚胎过程中几乎任何时刻的实验操作 发展。先前的实验表明，随着感觉轴突长成 肢体，它们对周围环境的暗示有不同的反应 以及其他轴突，与一些轴突关联并与其他轴突分离。 由细胞粘附分子（CAM）介导的优先粘附性， 有助于感觉轴突沿着适当的方向束动的能力 轴突并在向远端生长时形成神经特异性束。拟议的 研究将扩展之前的工作，检查束震、CAM 的作用， 和感觉轴突寻路中的环境线索。逆行标签， 抗体染色以区分感觉轴突和运动神经元 (MN) 轴突，以及 共聚焦显微镜将结合起来检查特定的轨迹 感觉轴突的亚型及其与其他轴突的空间关系 各种实验情境。具体来说，一些拟议的研究 将使用功能阻断抗体的注射来确定有多少 CAM（G4/L1、N-钙粘蛋白、DM-GRASP/SC1、axonin-1、NrCAM、神经成束蛋白和 F11） 影响感觉/MN 轴突混合、束颤、形成 神经特异性束，以及通过皮肤和肌肉感觉寻路 轴突。 EM 将用于确定感觉轴突是否在早期发生束束 阶段和 CAM 扰动之后。其他研究确定是否某些 正确分类感觉需要特定的肢体相关线索 轴突通常注定沿着不同的周围神经投射。一个 先前发现的重要意义是感觉神经元投射 沿着不同的末梢神经的神经在早期必定是不同的 阶段，因为它们的轴突首先向肢体延伸。因此，一些 拟议的研究将检查基因表达的差异 不同类型的感觉神经元。