Regulation of Drosophila Circadian Output Pathways

果蝇昼夜节律输出途径的调节

• 批准号: 6475332
• 负责人: JAE H PARK
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6475332
• 关键词: Drosophilidae; RNase protection assay; arthropod genetics; behavior test; biological signal transduction; circadian rhythms; ethology; gene expression; genetic regulation; high performance liquid chromatography; hormone regulation /control mechanism; immunocytochemistry; neurogenetics; neurons; neuropeptides; northern blottings; peptide hormone; photobiology

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?

描述（由申请人提供）：生理和行为的日常节奏