DROSOPHILA NEURAL DEVELOPMENT ROLE OF BIOGENIC AMINES

这项建议涉及有关分析发展的实验 生物胺系统及其在神经发育中的整体作用。 在生物胺的情况下，异常的神经递质水平已经被发现。 观察到与许多人类病理学相关（例如， 帕金森病、苯丙酮脲、精神分裂症）。 果蝇 黑腹，中枢神经系统（CNS）的神经缺陷，解剖 来自多巴脱羧酶基因缺陷的动物， 因此，已经观察到缺乏内源性5-羟色胺和多巴胺。 具体而言，拟议研究的目的是：1）进一步 多巴脱羧酶的神经解剖学和生物化学特性 缺陷型和野生型CNSs; 2）确定发育 观察到的扰动的病因学;和3） 神经缺陷 为了解决这些问题，实验策略， 依赖于基因工具的复杂使用，突变体和基因 将使用果蝇系统特有的镶嵌动物。 在 此外，目前可用于可视化的传统工具 将使用生物胺系统并表征神经元组织。 这些工具包括针对神经递质的抗体， 神经肽，儿茶酚胺组织荧光，放射性胺， 免疫组织化学和放射自显影。 该方法将有一个 强大的神经解剖学成分。 预计， 分子技术将提供更多的工具， 提高神经递质作用的因果分析的分辨率 在神经系统的发育和维持中。

This proposal involves experiments concerning the analysis of development of biogenic amine systems and their overall role in neural development. Aberrant neurotransmitter levels in the case of biogenic amines have been observed in association with a number of human pathologies (e.g. Parkinson's disease, phenylketonurea, schizophrenia). In Drosophila melanogaster, neural defects in the central nervous system (CNS), dissected from animals genetically deficient for the enzyme dopa decarboxylase and therefore, lacking endogenous serotonin and dopamine have been observed. Specifically, the aims of the proposed research are: 1) further neuroanatomical and biochemical characterization of the dopa decarboxylase deficient and the wild-type CNSs; 2) determination of the developmental etiology of the observed perturbations; and 3) causal analyses of the neural defects. To approach these questions, experimental strategies that depend on the sophisticated use of genetic tools, mutants and genetically mosaic animals, unique to the Drosophila system, will be used. In addition, conventional tools that are currently available to visualize biogenic amine systems and characterize neuronal tissues will be employed. These tools include antibodies raised against neurotransmitters and neuropeptides, catecholamine histofluorescence, radioactive amines, immunohistochemistry and autoradiography. The methodology will have a strong neuroanatomical component. It is anticipated that rapid advances in molecular techniques will provide additional tools that will further sharpen the resolution of causal analysis of the role of neurotransmitters in the development and the maintenance of the nervous system.