Regulation of Drosophila Circadian Output Pathways

描述(申请人提供)：生理和行为的日常节律 在地球上的大多数生命形式是由自然周期同步的(主要是 光：暗周期)，随后在恒定条件下自由运行 比如持续的黑暗。因此，这些节奏是由内部的 昼夜节律起搏器，使用身体波动的刺激来测量 随着时间的推移。生物钟紊乱导致严重的健康问题 在我们的社会中，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 (黑腹果蝇)有一些共同的特征，这表明 中央计时器自始至终都保存着 进化之路。然而，中央时钟的机制是如何 与下游目标进行通信，这些目标可能对 更直接的公开生理和行为节律，在很大程度上是未知的。 最近由我们领导的研究表明，一种神经肽，即分散色素的 因子(PDF)是起搏器产生的一种重要的昼夜节律信使 在果蝇中，神经元被称为侧向神经元。考虑到...的复杂性 在起搏系统中，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。我会的 我想研究AKH基因在人的昼夜节律调节中的作用 使用生化和分子神经遗传学工具的果蝇。我建议： 1.检验AKH基因表达受中枢调控的假说 计时系统。AKH基因产物在野生型周期中的昼夜节律吗 举止？如果是这样的话，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 昼夜节律行为节律。AKH细胞的靶向消融是否会导致 昼夜节律异常吗？AKH基因的过度表达和错误表达 打乱了正常的昼夜节律？

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?