REGULATION OF THE DOPA DECARBOXYLASE GENE

这项研究的目的是定义监管机制 果蝇的时间、组织和细胞特异性表达 黑素胃多巴脱羧酶基因，DDC，具有特异性 重视中枢神经系统中DDC的调节 (CNS)。这些研究是在果蝇身上进行的，因为 体外基因操作的结果可以很容易地检测出来 继生殖系基因整合后，强大的遗传 选择是可能的。然而，我们预计这些信息 关于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 适用于更高级别的系统。无论是转录还是后转录- 调控DDC表达的转录机制将是 学习。具有共同调控元件的其他基因 DDC将被分离和鉴定。基因选择将是 用于定义顺式和反式作用元件，调节 DDC转录本的交替剪接。突变的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5-羟色胺。生理和行为 将评估CNS DDC表达缺失的后果， 以及由于缺乏中枢神经系统而导致的差异表达基因 将分离DDC表达。这些菌株还将被用来 研究MPTP的作用机制，该化合物是一种 会在哺乳动物身上产生帕金森症症状。最后，我们会 试图通过表达来消除中枢神经系统中的特定细胞 它们里面有致命的细胞产物。

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.