ASSEMBLY OF A NEUROMUSCULAR UNIT IN C ELEGANS

这项工作的长期目标是阐明基因和 神经回路在大脑中组装的分子机制 发育中的神经系统。提议的项目将分析如何具体地 线虫产卵系统中的神经肌肉单位 优雅女装已经组装好了。 动物的神经系统是高度有序的神经系统的集合。 控制和协调动物行为的回路。至 了解这些神经电路是如何组装的，以及这些线路是如何 神经系统的图解最终取决于 了解生长轴突如何找到它们的靶细胞以及靶细胞是如何 把它们放到正确的位置。这个神经引导的问题和 目标定位在线虫身上得到了解决，线虫是一种提供 某些实验优势。每一个体细胞的起源和命运 已知，所有302个神经元的详细解剖和连接已被 描述，神经系统的整个接线图已经被 推断，而且这种动物是可以接受基因操纵的。 线虫的产卵系统是可访问的，并且定义得很清楚。这个 系统中每种细胞类型的发育可以选择性地通过 突变和/或通过激光微束消融。对这些问题的分析 惊慌失措的动物已经暗示了特定细胞在组装中的作用 产卵马达系统的。拟议研究的目标是 进一步定义指导所需的细胞和细胞相互作用 神经突起和肌肉在产卵过程中的位置。 这些细胞相互作用被破坏的突变体将被隔离， 这些突变应该识别编码和调节这些基因的基因 流程。这些基因的鉴定及其功能 对他们的产品进行表征可能会揭示一个神经肌肉单位 已经组装好了。在这个系统中阐明的机制可能揭示出一般的 神经回路的组装机制不仅在线虫中，而且在 其他生物也是如此。这些规则可能会让人深入了解人们有多紧张 在高等生物体的发育过程中，系统变得“连线错误”。

The long-term objective of this work is to elucidate the genetic and molecular mechanisms by which neural circuits are assembled in the developing nervous system. The proposed project will analyze how a specific neuromuscular unit in the egg-laying system of the nematode Caenorhabditis elegans is assembled. The nervous system of an animal is a highly ordered collection of neural circuits that control and coordinate the behavior of an animal. To understand how these neural circuits are assembled and how the wiring diagram of the nervous system is determined ultimately depends on understanding how growing axons find their targets and how target cells are positioned into their correct places. This problem of neuronal guidance and target positioning is being addressed in C. elegans, an animal that offers certain experimental advantages. The origin and fate of every somatic cell is known, detailed anatomy and connectivity for all 302 neurons have been described, the entire wiring diagram of the nervous system has been inferred, and the animal is amenable to genetic manipulations. The egg-laying system of C. elegans is accessible and well-defined. The development of each cell type in the system can be selectively perturbed by mutation and/or by ablation with a laser microbeam. Analysis of such perturbed animals has suggested a role for specific cells in the assembly of the egg-laying motor system. The goals of the proposed research are to define further the cells and cell interactions necessary for the guidance of the neuronal processes and the positioning of the muscles in egg-laying. Mutants will be isolated in which these cell interactions are disrupted, these mutations should identify the genes that encode and regulate these processes. The identification of these genes and the functional characterization of their products may disclose how one neuromuscular unit is assembled. The mechanisms elucidated in this system may reveal general mechanisms for assembly of neural circuits not only in C. elegans, but in other organisms as well. These rules may yield insights into how nervous systems become "miswired" during development in higher organisms.