DEVELOPMENT OF MOTONEURONAL CONNECTIVITY

运动神经连接的发展

• 批准号: 3401956
• 负责人: Monte Westerfield
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3401956
• 关键词: aquatic organism; axon; developmental genetics; electron microscopy; electrophysiology; embryo /fetus; fluorescent dye /probe; gap junctions; gene expression; genetic transcription; in situ hybridization; innervation; muscle transplantation; mutant; myoblasts; neurogenesis; neuromuscular junction; neurophysiology; radionuclide double label; regulatory gene; synapses; zebrafish

Proper nervous system function depends on precise contacts between nerve cells and their targets. The objective of this study is to learn how the development of specific synaptic connections is regulated. We propose cellular, molecular and genetic analyses of the interactions between particular motoneurons and muscle cells in an embryonic vertebrate, the zebrafish. By studying and perturbing the early development of these cells, we will learn how targets function in specifying the formation of synaptic connections. We propose three specific aims: a) We will identify the particular subset of muscle cells with which the motoneurons first interact and characterize their early development, using a variety of molecular markers. From this we will learn how they differentiate and when they express particular genes that may be important for their developmental functions. b) We will ablate and transplant these cells early in development to see if they function in the patterning of body muscle segments. c) We will characterize and study genes expressed by these muscle cells during early development to learn how they may function in the specification of neuromuscular synapses. Although much work has been done to describe how synapses form, very little is known about what regulates the formation of specific synaptic connections; that is, how does a neuron know which cells it should and should not innervate? In humans, neurons sometimes make mistakes. For example, there are a number of congenital defects (such as infantile Muscular Dystrophies) that are due to incorrect connections between nerve cells and their targets. By learning how these connections normally develop we will gain insights into what goes awry to cause developmental abnormalities.

正常的神经系统功能取决于神经和神经元之间的精确接触 细胞和它们的目标。 本研究的目的是了解 特定突触连接的发育受到调节。 我们提出 细胞，分子和遗传分析之间的相互作用 特别是运动神经元和肌肉细胞在胚胎脊椎动物， 斑马鱼 通过研究和扰乱这些早期的发展， 细胞，我们将学习如何在指定的目标功能的形成 突触连接 我们提出了三个具体目标：a）我们将确定 运动神经元首先与之接触的肌肉细胞的特殊亚群 互动和表征他们的早期发展，使用各种 分子标记 从中我们将了解它们是如何区分的，以及何时区分。 它们表达的特定基因可能对它们的发育很重要， 功能协调发展的B）我们将在早期消融并移植这些细胞， 看看它们是否在身体肌肉的模式中起作用 片段c）我们将描述和研究这些肌肉表达的基因 细胞在早期发展，以了解他们如何可能发挥作用， 神经肌肉突触的特化。 尽管已经做了很多工作来描述突触是如何形成的， 是什么调节了特定突触的形成 也就是说，一个神经元如何知道它应该和 不应该受到刺激？在人类中，神经元有时会犯错误。 为 例如，有一些先天性缺陷（如婴儿型）， 肌肉营养不良）是由于神经之间的连接不正确 细胞和它们的目标。 通过了解这些连接通常是如何 我们将深入了解什么是错误的，导致发展 异常