ASSEMBLY OF A NEUROMUSCULAR UNIT IN C ELEGANS

这项工作的长期目标是阐明遗传和 神经回路在大脑中组装的分子机制 神经系统发育。该项目将分析一个具体的 小杆线虫产卵系统中的神经肌肉单位 elegans组装好了。 动物的神经系统是一个高度有序的神经元集合， 控制和协调动物行为的电路。到 了解这些神经回路是如何组装的， 神经系统图的确定最终取决于 了解生长中的轴突如何找到它们的目标，以及目标细胞如何 把它们放在正确的位置上。神经元引导的问题， 目标定位在C中解决。优雅的动物， 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经被 描述，整个神经系统的布线图已经被描述为 推断，和动物是服从基因操纵。 对C. elegans是可访问的和定义明确的。的 系统中每种细胞类型的发育可以被选择性地干扰， 突变和/或用激光微束烧蚀。分析此类 受到干扰的动物提出了特定细胞在组装中的作用 产卵的运动系统。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 神经过程和肌肉在产卵过程中的位置。 将分离这些细胞相互作用被破坏的突变体， 这些突变应该可以识别出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 他们的产品的特征可能揭示了一个神经肌肉单位 组装完成。在这个系统中阐明的机制可能揭示一般的 不仅在C.优雅，但在 其他生物也是。这些规则可以让我们了解到 在高等生物的发育过程中，系统变得“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.