REGULATION OF THE DOPA DECARBOXYLASE GENE

本研究将研究顺式元件和反式作用因子， 控制果蝇多巴脱羧酶基因（Ddc）在 CNS中的特定神经元亚群。 特别令人感兴趣的是 鉴定的顺式元件和推定的反式因子调节表达， 血清素神经元的一个子集。 这个因子的作用， 基因xfh2，在Ddc表达和血清素的发展中， 多巴胺神经元将通过基因和 生物化学方法 与该区域结合的其他因素将 被孤立 在血清素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， 它们的调控区，并分离出可以被 用于表达代谢和发育重要的基因 特定细胞模式的产品。 似乎选择性剪接是一个主要的决定因素， 组织特异性基因表达CNS。 顺式元件和 将研究对Ddc选择性剪接重要的反式因子 在生物化学上使用细胞培养系统和在体内。 在这些研究中产生的许多菌株将具有改变的 血清素和多巴胺。 这些将被分析， 改变了生物钟和学习行为， 关于中枢神经系统区域中特定递质的作用。 这些 研究是在一个模型系统中进行的， 在脊椎动物系统中不可能操纵。 许多酶和 该系统的调节因子在果蝇之间是保守的， 脊椎动物，表明获得的信息可能是 通常与类似的脊椎动物系统相关。

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.