INTERMEDIATE FILAMENTS IN NEURAL DEVELOPMENT

神经发育中的中间丝

• 批准号: 3326945
• 负责人: LINDA M PARYSEK
• 金额: $ 13.96万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3326945
• 关键词: cell differentiation; complementary DNA; cytoskeletal proteins; developmental neurobiology; intermediate filaments; laboratory rat; nerve /myelin protein; neurofilament proteins; neurons; tissue /cell culture

The long-term objective of the work proposed here is to understand the role of intermediate filaments (IF) in neural development. IF are thought to be structurally important in the development and maintenance of cell morphology. Studies have shown that the expression of proteins that compose IF changes as cells differentiate. This data indicates that IF may be involved in functions specific to the differentiated state of cells or to the process of differentiation. The goals pertinent to the work described in this application are to study the importance of one particular IF protein the 57kD neural IF protein (NIFP) to differentiation in vivo and in vitro. The distribution of the 57kD NIFP will be examined during development of the rat in the embryonic and early postnatal period. The relationship of this protein to the ontogeny and differentiation of neurons will be examined in tissue sections using antibodies to the 57kD NIFP as probes. To determine the role of the 57kD NIFP in processes involved in differentiation, the effects of a disrupted IF network on nerve growth factor-induced differentiation in the neuron-like cell line PC12 will be determined. IF disruption will be accomplished via gene transfer of deletion mutants of the 57kD NIFP cDNA. The study of this neural IF protein is expected to yield information on neural development and the cellular components involved. These findings will have obvious relevance to the development of the normal embryo but also should add to our knowledge of the neuronal intermediate filaments. Analyses of the role of these structures in normal neuronal function should lead to an improved understanding of the processes leading to abnormal accumulations of IF. These accumulations are prominent pathologic findings in many important degenerative neurologic diseases.

这里提出的工作的长期目标是了解 中间丝（IF）在神经发育中的作用。 如果是 被认为在开发和维护中具有结构上的重要性 细胞形态学。研究表明，蛋白质的表达 当细胞分化时，IF 会发生变化。 这个数据表明 IF可能涉及特定于分化的功能 细胞状态或分化过程。 目标 与本申请中描述的工作相关的是研究 一种特定 IF 蛋白（57kD 神经 IF 蛋白）的重要性 （NIFP）在体内和体外分化。 57kD NIFP 的分布将在开发过程中进行检查 胚胎期和产后早期的大鼠。 关系 这种蛋白质对神经元个体发育和分化的影响将是 使用 57kD NIFP 抗体作为探针在组织切片中进行检查。 确定 57kD NIFP 在涉及的过程中的作用 分化，IF 网络中断对神经生长的影响 神经元样细胞系 PC12 中因子诱导的分化将是 决定。 IF 破坏将通过基因转移来完成 57kD NIFP cDNA 的缺失突变体。 对这种神经 IF 蛋白的研究预计将产生以下信息： 神经发育和所涉及的细胞成分。 这些发现 与正常胚胎的发育有明显的相关性，但 还应该增加我们对神经元中间丝的了解。 分析这些结构在正常神经元功能中的作用 应该导致对导致的过程有更好的理解 IF异常积累。 这些积累是突出的 许多重要的退行性神经系统疾病的病理学发现。