REGULATION OF THE DOPA DECARBOXYLASE GENE

本研究将研究顺式元件和反式作用因子 果蝇多巴脱羧酶基因(DDC)在大肠杆菌中的表达 中枢神经系统中特定的神经元亚群。特别值得关注的是一个 已鉴定的顺式元件和可能的反式因子调节表达 5-羟色胺神经元的一个子集。这个因素的作用，即同源结构域 基因xfh2在DDC表达和5-羟色胺和5-羟色胺的发育中的作用 多巴胺神经元将通过联合遗传和 生化方法。制约该地区的其他因素将 与世隔绝。在5-羟色胺和多巴胺中表达的其他基因 神经元将被分离和研究，两者都是为了比较分析 它们的监管区域，并分离出可以 用于表达新陈代谢和发育重要的基因 特定细胞模式的产品。 看起来，选择性剪接是一个主要的决定因素 组织特异性基因的表达。中枢神经系统。顺位元素和 将研究对DDC选择性剪接重要的反式因子 使用细胞培养系统和体内的生物化学。 在这些研究中产生的许多菌株将改变其水平 中枢神经系统神经元中的5-羟色胺和多巴胺。将对这些进行化验 改变昼夜节律和学习行为，潜在地产生洞察力 关于特定发射器在中枢区域的作用。这些 研究正在一个模型系统中进行，该模型系统允许实验 操纵在脊椎动物系统中是不可能的。许多酶和 该系统的调节因子在苍蝇和苍蝇之间是保守的 脊椎动物，这表明获得的信息很可能是 通常与类似的脊椎动物系统有关。

This research will study the cis-elements and trans-acting factors that control expression of the Drosophila dopa decarboxylase gene (Ddc)in specific neuronal subsets in the CNS. Of particular interest is an identified cis-element and putative trans-factor regulating expression in a subset of serotonin neurons. The role of this factor, the homeodomain gene xfh2, in Ddc expression and in the development of serotonin and dopamine neurons will be determined via a combined genetic and biochemical approach. Additional factors that bind to this region will be isolated. Additional genes expressed in serotonin and dopamine neurons will be isolated and studied, both for a comparative analysis of their regulatory regions, and to isolate regulatory cassettes that can be used to express metabolically and developmentally important genes products in specific cellular patterns. It appears that alternative splicing is a major determinant of tissue-specific gene expression in. the CNS. The cis-elements and trans-factors important for alternative splicing of Ddc will be studied biochemically using a cell culture system and in vivo. Many strains generated in these studies will have altered levels of serotonin and dopamine in defined CNS neurons. These will be assayed for altered circadian and learning behaviors, potentially yielding insights as to the roles of particular transmitters in regions of the CNS. These studies are being performed in a model system that allows experimental manipulation not possible in vertebrate systems. Many of the enzymes and regulatory factors of this system are conserved between flies and vertebrates, indicating that the information gained is likely to be generally relevant to analogous vertebrate systems.