DEVELOPMENTAL GENETICS OF THE C ELEGANS DAUER LARVA

拟议的研究是对基因控制的继续调查。 在一个简单的动物模型中的发育。方法是应用基因， 用显微、超微结构和生化方法进行详细分析 在人的生命周期中存在着胚胎后的“发育开关” 线虫，秀丽线虫。这一转变在第二个问题上表现出来。 幼虫蜕皮，当饥饿或过度拥挤的条件可能导致 达尔幼虫的形成，一种发育停滞、不取食的幼虫 舞台。总的目标是确定遗传病的基础 达尔幼虫形成和恢复的发展计划，以及 细胞周期调控的分子和生理机制 发展规划。提出了具体的目标，分为六个 补充调查领域：(A)生化和物理领域 生物活性物质的分析，包括一种新的 发现了信息素，它作为环境线索影响着 在两条不同的发展道路之间作出决定，(B) 突变体的选择和遗传分析，无论是受 L2蜕皮前的发育决定，受影响的时间 导致达尔幼虫的发育顺序，或在特定情况下受影响 达尔幼虫形态发生的方面，(C)电子显微镜 感觉神经解剖学或腺体解剖的特征 被怀疑有感觉缺陷或分泌的特定突变体 异常；(D)发育研究，旨在测试 发育的幼虫对特定的环境刺激，并确定 (E)神经学研究 旨在识别特定的细胞，这些细胞在过程中发挥作用 进入或退出Dauer阶段，以及(F)分子研究 确定与以下相关的转录调控的范围和时间 交替的发育顺序。将使用新方法来 简化遗传选择，并允许更快速的遗传分析 变种人。生理水平上的野生型发育分析， 在发育调控基因转录本的水平上， 为突变表型的分析提供了新的参照系。

The proposed research is a continued investigation of the genetic control of development in a simple animal model. The approach is to apply genetic, microscopic, ultrastructural and biochemical methods to a detailed analysis of a postembryonic "developmental switch" in the life cycle of the nematode, Caenorhabditis elegans. The switch is manifested at the second larval molt, when starvation or overcrowded conditions may result in the formation of dauer larvae, a developmentally arrested, non-feeding larval stage. The overall aim is to determine the genetic basis of the developmental program for dauer larva formation and recovery, and the molecular and physiological mechanisms for the implementation of the developmental program. Specific goals are proposed which fall into six complementary areas of investigation: (a) biochemical and physical analysis of the biologically active substances, including a newly discovered pheromone, which act as environmental cues influencing the decision made between the two alternate developmental pathways, (b) selection and genetic analysis of mutants, either affected in the developmental decision preceding the L2 molt, affected in the timing of the developmental sequence leading to the dauer larvae, or affected in specific aspects of dauer larva morphogenesis, (c) electron microscopic characterization of the sensory neuroanatomy, or glandular anatomy, of specific mutants suspected to have sensory defects or secretory abnormalities, (d) developmental studies designed to test the response of developing larvae to specific environmental stimuli, and determine the timing of commitment to that to that response, (e) neurological studies designed to identify the specific cells which function in the process of entry into, or exit from, the dauer stage, and (f) molecular studies to determine the extent and timing of transcriptional controls associated with the alternate developmental sequences. New methods will be used to simplify genetic selection, and permit more rapid genetic analysis of mutants. The analysis of wild-type development at the physiological level, and at the level of developmentally regulated gene transcripts, will provide new frames of reference for the analysis of mutant phenotypes.