FORMATION AND ELIMINATION OF NERVE-MUSCLE SYNAPSES

神经肌肉突触的形成和消除

• 批准号: 3395470
• 负责人: JEFFREY L DENBURG
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395470
• 关键词: axon; axon reaction; basement membrane; cell adhesion; cell cell interaction; cockroach; developmental neurobiology; extracellular matrix; genetic regulation; glycoproteins; innervation; interneurons; laboratory mouse; laboratory rat; molecular cloning; monoclonal antibody; motor neurons; muscle; nervous system regeneration; neural growth associated protein; neurochemistry; neurogenesis; neuromuscular junction; neuronal guidance; nonmammalian vertebrate embryology; nucleic acid sequence; protein purification; synapses; synaptogenesis

For the nervous system to function, signals are conducted and transmitted in neuronal circuits that reflect the pattern of connections between the cells. The formation of these innervation patterns during development requires the following cellular phenomena; axon elongation, guidance of axon growth and target recognition. The long term goal of this research is to understand these at the molecular level. Axon elongation is a highly specialized task and it is likely that there are molecules whose main function is to mediate this growth. Such molecules might only be present in the neuron when it is growing an axon during embryonic development of during axon regeneration in adults. A monoclonal antibody (MAb) has been produced that binds to such a protein. The molecular characteristics, the function and the mechanisms regulating cellular levels of this molecule will be studied. For a growing axon to reach the vicinity of its target there must be cues in the environment which guide its growth. The first axons in the insect leg grow proximally in response to cues in the extracellular matrix/basement membrane. It has been hypothesized that such cues are distributed in a gradient along the proximal-distal axis of the leg. MAbs have been produced that bind to antigens with such a distribution. The molecular characteristics and function of these antigens will be studied. The existence of target recognition implies that there are biochemical distinctions among the various neurons and targets. MAbs have been produced that bind to the surfaces of axon terminals of some neurons and not others. These candidate neuronal recognition molecules will be biochemically characterized, their function determined and used to study the role of target recognition in axon regeneration. These experiments are done in the neuromuscular system of the cockroach, Periplaneta americana. This has been an excellent model system. Its relatively simple structure and extreme immunogenicity have enabled the production of the immunological probes to an unusual and interesting set of molecules. Because the molecular bases of these developmental events are likely to be similar in vertebrate neurons, a search for homologous molecules will be made. Information on axon elongation and target recognition are relevant to attempts to increase the probability of obtaining successful axon regeneration in humans. Such knowledge would also be helpful for the treatment of paraplegia, neuromuscular disorders, multiple sclerosis and other neurological disorders involving injury such as strokes and head injury.

为了使神经系统发挥作用，信号被传导和传输 反映神经元之间连接模式的神经元回路 细胞。 这些神经支配模式在发育过程中的形成 需要以下细胞现象；轴突伸长，引导 轴突生长和目标识别。 这项研究的长期目标是 在分子水平上理解这些。 轴突伸长是一项高度专业化的任务，很可能存在 是其主要功能是介导这种生长的分子。 这样的 分子可能只在神经元生长轴突时才存在 在成人轴突再生期间的胚胎发育期间。 一个 已经生产出与这种蛋白质结合的单克隆抗体（MAb）。 分子特性、功能及调控机制 将研究该分子的细胞水平。 对于正在生长的轴突到达其目标附近必须有线索 在引导其生长的环境中。 昆虫的第一个轴突 腿响应细胞外信号向近端生长 基质/基底膜。 据推测，此类线索是 沿着腿的近端-远端轴呈梯度分布。 单克隆抗体 已经产生了与具有这种分布的抗原结合的抗原。 这 将研究这些抗原的分子特征和功能。 目标识别的存在意味着生化作用的存在 各种神经元和目标之间的区别。 单克隆抗体已 产生的结合到一些神经元轴突末端的表面， 不是其他人。 这些候选神经元识别分子将是 进行生化表征，确定其功能并用于研究 目标识别在轴突再生中的作用。 这些实验是在蟑螂的神经肌肉系统中进行的， 美洲大蠊。 这是一个优秀的模型系统。 它是 相对简单的结构和极端的免疫原性使得 生产针对一组不寻常且有趣的免疫学探针 分子。 因为这些发育事件的分子基础是 脊椎动物神经元中可能相似，寻找同源 将会产生分子。 有关轴突伸长和目标的信息 认可与增加可能性的尝试有关 在人类中获得成功的轴突再生。 这样的知识将 也有助于治疗截瘫、神经肌肉疾病、 多发性硬化症和其他涉及损伤的神经系统疾病，例如 如中风和头部受伤。