DEVELOPMENT OF MOTONEURONAL CONNECTIVITY

神经系统的正常功能依赖于神经之间的精确接触 细胞和它们的靶子。这项研究的目的是了解 特定突触连接的发展是受调控的。我们建议 相互作用的细胞、分子和遗传学分析 胚胎脊椎动物中特殊的运动神经元和肌肉细胞 斑马鱼。通过研究和扰乱这些早期的发展 细胞，我们将学习目标如何在指定 突触连接。我们提出了三个具体目标：a)我们将确定 运动神经元最先与之相连的肌肉细胞的特定子集 互动和描述他们的早期发展，使用各种 分子标记。由此，我们将了解它们如何区分以及何时 它们表达特定的基因，这些基因可能对它们的发育至关重要 功能。B)我们将在早期切除和移植这些细胞 发育以观察它们是否在身体肌肉的模式中起作用 细分市场。C)我们将表征和研究这些肌肉表达的基因 细胞在早期发育过程中，以了解它们如何在 神经肌肉突触的规范。 尽管已经做了很多工作来描述突触是如何形成的，但很少有 已知是什么调节了特定突触的形成 连接；也就是说，神经元如何知道它应该和 不应该神经紧张吗？在人类身上，神经元有时会犯错误。为 例如，有一些先天缺陷(如婴儿 肌萎缩症)，这是由于神经之间的错误连接 细胞和它们的靶子。通过了解这些连接通常是如何 发展我们将深入了解是什么出了问题导致发展 异常现象。

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.