Monoamine Functions in Drosophila Female Reproduction

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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.