FORMATION AND ELIMINATION OF NERVE/MUSCLE SYNAPSES

神经/肌肉突触的形成和消除

• 批准号: 2262609
• 负责人: JEFFREY L DENBURG
• 金额: $ 20.36万
• 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/2262609
• 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.

为使神经系统发挥作用，信号被传导和传递 在神经元回路中，反映了 细胞。在发育过程中这些神经支配模式的形成 需要下列细胞现象；轴突延长，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。 轴突延长是一项高度专业化的任务，很可能有 是其主要功能是调节这种生长的分子。是这样的 分子可能只在神经元长出轴突时才存在。 在胚胎发育过程中，在成体轴突再生期间。一个 已经产生了与这种蛋白质结合的单抗(MAb)。 其分子特征、功能及其调控机制 这种分子的细胞水平将被研究。 生长中的轴突要到达其目标附近，必须有线索 在引导它成长的环境中。昆虫中的第一个轴突 腿部近端生长对细胞外暗示的反应 基质/基底膜。据推测，这样的线索是 沿着腿的近端-远端轴线呈梯度分布。单抗 已经产生了与具有这种分布的抗原结合的物质。这个 这些抗原的分子特征和功能将被研究。 目标识别的存在意味着有生化的 不同神经元和靶点之间的区别。单抗一直是 产生与某些神经元轴突终末表面结合的物质 不是其他人。这些候选神经元识别分子将是 生化表征、功能测定及用于研究 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。它的 相对简单的结构和极强的免疫原性使 一组不同寻常和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很可能是相似的，寻找同源的 分子将会被制造出来。关于轴突延长和靶点的信息 识别与试图增加 成功地在人类体内获得轴突再生。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疾病 比如中风和头部受伤。