Regulation of Drosophila Circadian Output Pathways

描述（由申请人提供）：生理和行为的日常节律 地球上大多数生命形式都是由自然周期（主要是 光：暗循环），并随后在恒定条件下自由运行 比如持续的黑暗因此，这些节奏是由内部驱动的 昼夜节律起搏器使用物理波动刺激来测量 时间的流逝生物钟紊乱会导致严重的健康问题 包括时差、失眠和轮班相关的疾病。 哺乳动物和果蝇的分子中枢时钟机制 （果蝇）有许多共同的特征，这表明， 中央计时装置长期保存， 然而，中央时钟的机制 与下游目标进行沟通，这些目标可能对 更直接的生理和行为节奏，在很大程度上是未知的。 最近我们领导的研究表明，一种神经肽， 因子（PDF）是一个重要的昼夜信使来自起搏器 神经元，在果蝇中称为侧神经元。考虑到 起搏系统应该有不止一个信使分子 间接证据表明，一种神经肽，脂肪运动激素 (AKH)可能参与昆虫的昼夜节律输出途径。我会 我想研究AKH基因在调节昼夜节律中的作用， 利用生物化学和分子神经遗传学工具研究果蝇。我提议： 1.验证AKH基因表达受中枢神经系统调控的假设。 计时系统野生型AKH基因产物是否在昼夜节律中循环 举止？如果是这样，时钟突变会影响这种循环吗？AKH基因在哪里 表达？时钟转录因子调控AKH基因表达吗？ 2.检验AKH表达神经元的作用涉及 昼夜行为节律。AKH细胞的靶向消融是否会导致 异常的昼夜行为AKH基因的过度表达和错误表达 扰乱正常的昼夜节律

DESCRIPTION (provided by applicant): Daily rhythms of physiology and behavior in most life forms on Earth are synchronized by natural cycles (mainly light:dark cycles), and are subsequently free-run under constant conditions such as constant darkness. Thus these rhythms are driven by the internal circadian pacemakers that use the physically fluctuating stimuli to measure the passage of time. Disruptions of biological clock cause severe health problems in our society, including jet-lag, insomnia, and shiftwork-related illnesses. The molecular central clock-ticking mechanisms in mammals and fruit flies (Drosophila melanogaster) share a number of common features, suggesting that the central time-keeping apparatus has been conserved throughout long evolutionary path. However, the mechanisms of how the central clocks communicate with the downstream targets that are likely responsible for the overt physiology and behavioral rhythms more directly, are largely unknown. Recent studies led by us revealed that a neuropeptide, pigment-dispersing factor (PDF) is an important circadian messenger derived from the pace-maker neurons, called Lateral Neurons in Drosophila. Considering the complexity of the pace-making system, there should be more than one messenger molecule. Circumstantial evidence suggests that a neuropeptide, adipokinetic hormone (AKH), could be involved in the circadian output pathways in insects. I would like to examine the role of AKH gene in the regulation of circadian rhythms in Drosophila using biochemical and molecular neurogenetic tools. I propose to: 1. Test the hypothesis that AKH gene expression is regulated by central clock-ticking system. Do AKH gene products in wild type cycle in a circadian manner? If so, do clock mutations affect this cycling? Where is the AKH gene expressed? Do clock transcription factors regulate AKH gene expression? 2. Test the hypothesis that the roles of AKH-expressing neurons involve the circadian behavioral rhythms. Does the targeted-ablation of the AKH cells cause abnormal circadian behaviors? Do the over- and misexpression of AKH genes disrupt normal circadian rhythms?