Regulatory Mechanisms of Drosphilia Tyrosine Hydroxylase

Lay摘要Proposal#：IBN-9816566PI名称：Wendi Neckameyer多巴胺在果蝇黑腹果蝇的几种生理环境中都是必需的，它在发育、生殖和行为途径中作为信号分子发挥作用。鉴于多巴胺的多重作用，在动物一生中的不同时间，不同组织中的多巴胺水平必须得到精确的调节。行为异常可能源于正常的多巴胺能神经传递的中断，或者来自异常发育的组织。为了区分多巴胺的这两个基本角色，该应用程序建议识别当多巴胺水平在发育过程中被扰乱时受到影响的成人行为。第二个目标是确定编码多巴胺合成限速步骤的基因正常表达所需的DNA序列元件。中枢神经系统内多巴胺能传递的特定扰动对于最终阐明多巴胺在行为调节中的作用至关重要。多巴胺的多种信号作用既新颖又重要，而且似乎在进化上是保守的。这项提案中概述的实验展示了如何在几种生理环境中招募相同的信号分子使用，并可能对认知病理的病因学产生深远的影响，包括帕金森氏症、精神分裂症和抑郁症。

LAY ABSTRACTProposal #: IBN-9816566PI Name: Wendi NeckameyerDopamine is required in several physiological contexts in the fruit fly Drosophila melanogaster, where it functions as a signaling molecule in developmental, reproductive and behavioral pathways. Given its multiple roles, the levels of dopamine must be precisely regulated in diverse tissues at different times throughout the life of the animal. Behavioral abnormalities may arise from disruption of normal dopaminergic neurotransmission, or from abnormally developed tissues. To distinguish between these two essential roles for dopamine, this application proposes to identify adult behaviors that are affected when dopamine levels are disrupted during development. A second goal is to identify the DNA sequence elements necessary for normal expression of the gene which encodes the rate-limiting step in dopamine synthesis. Specific perturbation of dopaminergic transmission within the central nervous system is critical for eventual elucidation of the role of dopamine in the modulation of behaviors. The multiple signaling roles for dopamine are both novel and vital, and appear to be evolutionarily conserved. The experiments outlined in this proposal demonstrate how the same signaling molecule may be recruited for use in several physiological contexts, and may have profound implications for the etiology of cognitive pathologies, including Parkinson's disease, schizophrenia, and depression.