Monoamine Functions in Drosophila Female Reproduction

描述（由申请人提供）：章鱼胺（OA）是无脊椎动物中的主要单胺，其功能类似于哺乳动物的去甲肾上腺素（NE）。果蝇OA受体（OAMB）激活cAMP和细胞内钙增加，不仅在脑和胸腹神经节的神经元亚群中高度富集，而且在雌性生殖系统中也高度富集。为了研究OAMB的生理功能，我们产生了OAMB突变体，包括亚型和无效等位基因。值得注意的是，oamb突变的雌性在排卵方面有缺陷，因此在卵巢中异常保留了成熟的卵子。通过使用强大的遗传工具和大量的果蝇资源，拟议的研究旨在确定OAMB调节排卵的解剖部位以及与OAMB在此过程中功能性相互作用的下游效应物。这将主要通过采用GAL 4/UAS二元表达系统和遗传抑制基因筛选来实现。从拟议和后续研究中获得的知识将有助于解开OAMB和其他肾上腺素能受体（AR）调节果蝇和其他动物排卵的生理和细胞机制。例如，NE通过作用于包括人类在内的哺乳动物的神经和生殖系统中的不同AR，对雌性生殖的许多方面产生深远的影响。此外，通常用于控制高血压、哮喘和抑郁症的药物靶向或极大地影响肾上腺素能系统。考虑到果蝇和哺乳动物之间的关键分子和信号转导途径的显着功能保守，从果蝇的拟议研究中获得的信息可能会增强我们对肾上腺素能系统如何影响人类生殖生理和健康的理解。

DESCRIPTION (provided by applicant): Octopamine (OA) is a major monoamine in invertebrates and is functionally similar to norepinephrine (NE) of mammals. The Drosophila OA receptor (OAMB) activates cAMP and intracellular calcium increases and is highly enriched not only in subsets of neurons in the brain and the thoracico-abdominal ganglion, but also in the female reproductive system. To investigate OAMB's physiological functions, we generated oamb mutants including hypomorphic and null alleles. Remarkably, oamb mutant females were defective in ovulation and thus contained abnormally retained mature eggs in their ovaries. By employing powerful genetic tools and tremendous resources of Drosophila, the proposed studies are aimed at identifying the anatomical site(s) in which OAMB regulates ovulation and the downstream effectors that functionally interact with OAMB for this process. These will be primarily accomplished by adopting the binary GAL4/UAS expression system and the genetic suppressor screen. Knowledge obtained from the proposed and follow-up studies will help unravel physiological and cellular mechanisms by which OAMB and perhaps other adrenergic receptors (ARs) regulate ovulation in Drosophila and other animals. NE, for example, exerts profound effects on many aspects of female reproduction by acting on distinct ARs in nervous and reproductive systems of mammals including humans. Moreover, drugs commonly used for the control of hypertension, asthma and depression target or greatly affect adrenergic systems. Considering a remarkable functional conservation of key molecules and signal transduction pathways between Drosophila and mammals, information obtained from the proposed studies in Drosophila may enhance our understanding of how adrenergic systems influence reproductive physiology and health in humans.