REGULATION OF THE DOPA DECARBOXYLASE GENE

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This research is aimed at defining mechanisms regulating the temporal, tissue- and cell-specific expression of the Drosophila melanogaster dopa decarboxylase gene, Ddc, with particular emphasis on regulation of Ddc in the central nervous system (CNS). These studies are being performed in Drosophila, since the results of in vitro genetic manipulation can be readily assayed following germline gene integration, and powerful genetic selections are possible. However, we expect that the information derived regarding both control of cell-specific gene expression, and on the functions of biogenic amines in the nervous system will be applicable to higher systems. Both transcriptional and post- transcriptional mechanisms regulating Ddc expression will be studied. Other genes sharing common regulatory elements with Ddc will be isolated and characterized. Genetic selections will be used to define cis- and trans-acting elements regulating the alternate splicing of Ddc transcripts. Mutant Ddc genes showing altered regulatory patterns will be used to elucidate the physiological role of the potential neurotransmitters dopamine and serotonin produced by Ddc. The physiological and behavioral consequences of a deficit of CNS Ddc expression will be assessed, and genes differentially expressed as a result of a lack of CNS Ddc expression will be isolated. These strains also will be used to study the mechanism of action of MPTP, a compound that produces Parkinonian symptoms in mammals. Finally, we will attempt to eliminate particular cells in the CNS by expressing cell-lethal products within them.