REGULATION OF THE DOPA DECARBOXYLASE GENE

这项研究旨在确定调节 果蝇的时间、组织和细胞特异性表达 黑腹果蝇多巴脱羧酶基因，Ddc， 强调中枢神经系统中Ddc的调节 （CNS）。 这些研究是在果蝇中进行的， 体外遗传操作的结果可以容易地测定 继生殖系基因整合，和强大的遗传 选择是可能的。 不过，我们希望 从细胞特异性基因表达的控制， 以及生物胺在神经系统中的作用， 适用于更高的系统。 转录和后 调控Ddc表达的转录机制将是 研究了 其他基因共享共同的调控元件， Ddc将被隔离和表征。 基因选择将是 用于定义顺式和反式作用元件， Ddc转录物的选择性剪接。 突变Ddc基因显示 改变的监管模式将被用来阐明 潜在神经递质多巴胺的生理作用 和DDC产生的血清素 生理和行为 将评估CNS Ddc表达缺陷的后果， 以及由于缺乏CNS而差异表达的基因， Ddc表达将被分离。 这些菌株也将用于 研究MPTP的作用机制， 在哺乳动物中产生帕金森症状。 最后我们将 试图通过表达 细胞内的致命物质

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.