FORMATION AND ELIMINATION OF NERVE-MUSCLE SYNAPSES

神经肌肉突触的形成和消除

• 批准号: 3395465
• 负责人: JEFFREY L DENBURG
• 金额: $ 20.3万
• 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/3395465
• 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; 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 在神经元回路中，反映了神经元之间的连接模式， 细胞 在发育过程中这些神经支配模式的形成 需要以下细胞现象：轴突伸长， 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， 是主要功能是调节这种生长的分子。 等 分子可能只在神经元轴突生长时才存在于神经元中 在胚胎发育过程中或在成年人的轴突再生过程中。 一 已经产生了与这种蛋白质结合的单克隆抗体（MAb）。 其分子特征、功能及调控机制 将研究该分子的细胞水平。 对于一个生长中的轴突来说，要到达它的目标附近， 引导它成长的环境。 昆虫的第一个轴突 腿向近端生长，以响应细胞外的线索， 基质/基底膜。 据推测，这些线索是 沿腿的近端-远端轴沿着以梯度分布。 mAbs 已经产生了与具有这种分布的抗原结合的抗体。 的 将研究这些抗原的分子特征和功能。 靶点识别的存在意味着存在生物化学 不同的神经元和目标之间的区别。 mab已经 产生的，结合到一些神经元的轴突末端的表面， 而不是其他人 这些候选的神经元识别分子将被 生物化学特征，其功能确定并用于研究 靶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 这是一个很好的模型系统。 其 相对简单的结构和极端的免疫原性使得 针对一组不寻常且有趣的免疫探针的生产 分子。 因为这些发育事件的分子基础是 在脊椎动物神经元中可能是相似的，寻找同源的 分子将被制造出来。 轴突伸长和靶点信息 承认是相关的尝试，以增加的概率， 在人体内成功再生轴突。 这样的知识， 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， 中风和头部受伤