SENSORY AXON PATHFINDING

感觉轴突寻路

• 批准号: 6539835
• 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/6539835
• 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（逐字从申请人的摘要中）： 这项研究是了解轴突如何选择正确的途径 在开发过程中。适当的探路对发展至关重要 个人，因为如果轴突找不到正确的目标，他们将不会 建立适当的突触连接，而神经系统不会 正常运行。这项研究重点是感官神经元支配 小鸡后肢是因为使用如此易于访问的系统 在胚胎中几乎任何时候都有促进实验操作 发展。先前的实验表明，随着感觉轴突的成长 肢体，他们对周围环境中的提示有所不同 以及其他轴突，与某些轴突相关并与其他轴突分离。 优先粘附，由细胞粘附分子（CAM）介导， 有助于感官轴突沿适当的能力引起的能力 轴突在远端生长时形成神经特异性束。提议 研究将扩展以前的工作，以研究着迷，凸轮的作用 和感官轴突探索中的环境提示。逆行标签， 抗体染色以区分感觉神经元（MN）轴突，以及 共聚焦显微镜将合并以检查特定的轨迹 感觉轴突的亚型及其与其他轴突的空间关系 各种实验情况。具体而言，一些提出的研究 将使用功能阻滞抗体的注射来确定几种 凸轮（G4/L1，N-钙粘蛋白，DM-GRASP/SC1，AXONIN-1，NRCAM，NEUROFASCIN和F11） 影响感官/MN轴突互和混合，着迷，形成 神经特异性束，皮肤和肌肉感觉 轴突。 EM将用于确定感觉轴突是否早期出现 阶段和凸轮扰动之后。其他研究决定了是否某些 正确分类的感觉需要特定的肢体相关提示 轴突通常注定要沿着不同的周围神经发射。一个 先前发现的重要含义是感觉神经元投射 沿着不同的外围神经必须在早期彼此不同 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。