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.
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