GENETIC ANALYSIS OF CHEMOSENSATION IN C ELEGANS

这项研究的目标是了解细胞、遗传、 和分子机制的化学感应反应的道尔诱导 秀丽隐杆线虫信息素Dauer幼虫是一种发育中的 不同的替代第三幼虫阶段（L3），专门用于长期- 在恶劣的条件下生存。正常L3和 Dauer幼虫主要通过化学感觉评估来控制， 环境浓度的一种分泌的诱导信息素。更 已经鉴定出25个以上的基因控制着dauer过程， 形成，它们被置于一个复杂的上位途径。一些 这些基因中的一个与化学感受过程本身有关， 其他的则可能在化学感觉的下游起作用以激活dauer- 幼虫发育程序这项建议集中在基因上， 与道尔信息素的功能和发育有关 化学感受细胞一个目的是严格测试感官的作用， 这些神经元与控制信息素反应有关。 信息素反应性将在动物中测量，其中个体 已识别的神经元已被激光微束消除。另一 目的是完成对重要基因突变的彻底搜索， 这些感觉细胞的功能和发育。基因突变 已经涉及信息素化学感觉将被用来识别 其他这样的基因使用各种经典的遗传方法。一 daf-11基因已经与信息素的产生过程有着密切的关系 chemosensation，将通过转座子标签克隆。各种 分子生物学和遗传学方法将被用来定义 daf-11的功能，包括DNA序列分析、基因产物 定位和遗传嵌合体分析。 另一个基因daf-19， 参与了大量感觉神经元的发育，包括 控制着Dauer的形成。daf-19将使用详细的 遗传和物理绘图以及DNA转化。克隆的基因将 用于测试daf-19参与开发 感觉细胞的DNA序列分析和表达研究。 感觉调制的dauer形成的C。elegans提供了一个很好的 感官和环境影响调查模型 发展将广泛的基因分析应用于 并在单个神经元上定义感觉通路 水平是独一无二的。此外，对dauer信息素的反应是一个模型， 化学感觉的一般过程，目前很差， 明白

The goal of the proposed research is to understand the cellular, genetic, and molecular mechanisms of chemosensory response to the dauer-inducing pheromone of Caenorhabditis elegans. The dauer larva is a developmentally distinct alternative third-larval stage (L3) that is specialized for long- term survival under harsh conditions. The choice between the normal L3 and the dauer larva is controlled primarily by chemosensory assessment of the environmental concentration of a secreted dauer-inducing pheromone. More than 25 genes have been identified that control the process of dauer formation and they have been placed into a complex epistasis pathway. Some of these genes are implicated in the chemosensory process per se, while others probably act downstream of chemosensation to activate the dauer- larval developmental program. This proposal concentrates on the genes implicated in the function and development of the dauer pheromone chemosensory cells. One aim is to rigorously test the role of sensory neurons that have been implicated in controlling pheromone response. Pheromone responsiveness will be measured in animals in which individual identified neurons have been eliminated with a laser microbeam. Another aim is to complete a thorough search for mutations in genes important for the function and development of these sensory cells. Mutations in genes already implicated in pheromone chemosensation will be used to identify other such genes using a variety of classical genetic approaches. One gene, daf-11, already implicated specifically in the process of pheromone chemosensation, will be cloned by transposon tagging. A variety of molecular biological and genetic approaches will be taken to defining the function of daf-11, including DNA sequence analysis, gene product localization, and genetic mosaic analysis. Another gene, daf-19, is implicated in the development of a large set of sensory neurons, including those controlling dauer formation. daf-19 will be cloned using detailed genetic and physical mapping and DNA transformation. The cloned gene will be used to test the involvement of daf-19 in the development of the sensory cells by DNA sequence analysis and expression studies. Sensory modulation of dauer formation in C. elegans provides an excellent model for the investigation of sensory and environmental influences on development. The opportunity to both apply extensive genetic analysis to such a problem and to define the sensory pathway at the single neuron level is unique. In addition, response to dauer pheromone is a model for the general process of chemosensation, which is currently poorly understood.