GENETICS OF PTERIDINE FUNCTION IN DROSOPHILA DEVELOPMENT

拟议研究的目标是(1)确定 黑腹果蝇神经发育过程中的出拳轨迹 系统和(2)利用这个具有良好遗传特征的基因座 启动对这些必需的监管组件的剖析 通过搜索与之相互作用的基因和基因产物来发挥功能 PU。第一个目标将通过对蒲公子的刻画来实现 在神经细胞中的转录和蛋白表达，阐明 蒲氏神经递质的结构及神经递质的检测 Pu基因突变对神经的形态和生化影响 发展。第二个目标将通过寻找可能性来实现 Pu与已知有表达模式的基因之间的相互作用 或与Pu相似的突变表型，并通过执行遗传 特定Pu的抑制子和基因外互补的筛选 突变。PING编码蝶啶生物合成酶GTP 环水解酶，催化表达的第一步 调节性辅因子四氢生物蝶呤。四氢生物蝶呤。 四氢生物蝶呤是调节血管紧张素转换酶基因表达所必需的 儿茶酚胺和5-羟色胺。在人类中，导致GTP丢失的突变 环水解酶活性的特征是不能合成这些 神经递质，导致过早死亡。对哺乳动物的研究也是如此 在细胞信号的调节相互作用中牵涉到这个辅因子 在免疫和神经细胞中运行的系统。这些角色似乎是 血清、尿液和尿液中的蝶呤类药物含量极高的基础 HIV相关患者的脑脊液分析 神经系统症状和各种增生性疾病。我们的工作 揭示了果蝇和哺乳动物中强烈的同源功能，以及一种 哺乳动物和哺乳动物之间的序列高度保守 果蝇GTP环水解酶。预计这一身份证明 果蝇中参与功能和功能的其他成分 神经过程中涉及的调节相互作用需要 蝶呤类药物将有助于更好地全面理解这一重要的 神经发育的特点。

The goals of the proposed research are (1) to define the functions of the Punch locus of Drosophila melanogaster in the developing nervous system and (2) to use this genetically well-characterized locus to initiate a dissection of regulatory components necessary for these functions by searching for genes and gene products that interact with Pu. The first goal will be achieved through a characterization of Pu transcript and protein expression in neural cells, elucidation of the structure of the neural products of Pu and the examination of the morphological and biochemical effects of mutations in Pu on neural development. The second goal will be achieved by searching for possible interactions between Pu and known genes that have patterns of expression or mutant phenotypes that parallel those of Pu and by performing genetic screens for suppressors and extragenic concomplementors of particular Pu mutations. Punch encodes the pteridine biosynthetic enzyme, GTP cyclohyrolase, which catalyzes the first step in the expression of the regulatory cofactor, tetrahydrobiopterin. Tetrahydrobiopterin. Tetrahydrobiopterin is required for an modulates the expression of the catecholamines and serotonin. In humans, mutations causing loss of GTP cyclohydrolase activity are characterized by failure to synthesize these neurotransmitters, resulting in early death. Work in mammals also implicates this cofactor in regulatory interactions in cell signaling systems operating in immune and neural cells. These roles appear to be the basis for very high levels of pteridines in the serum, urine and cerebrospinal fluid of patients suffering from HIV-associated neurological symptoms and a variety of proliferative diseases. Our work reveals strongly homologous functions in Drosophila and mammals and a high degree of conservation between the sequence of mammalian and Drosophila GTP cyclohydrolase. It is anticipated that the identification of other components in Drosophila that participate in functional and regulatory interactions involved in neural processes requiring pteridines will lead to a better general understanding of this important feature of neural development.