GENETICS OF PTERIDINE FUNCTION IN DROSOPHILA DEVELOPMENT

本研究的目标是：（1）明确 黑腹果蝇Punch基因座在神经发育中的作用 系统和（2）使用这种遗传上良好表征的基因座， 开始解剖这些所需的调节成分， 通过寻找基因和基因产物来发挥作用， PU.第一个目标将通过对浦的定性来实现 转录本和蛋白质表达，阐明 Pu神经产物的结构及对神经元的检测 Pu基因突变对神经细胞形态和生化的影响 发展第二个目标将通过寻找可能的 Pu和已知基因之间的相互作用， 或突变表型，平行那些钚，并通过执行遗传 筛选特定Pu的抑制子和基因外互补子 突变。穿孔编码蝶啶生物合成酶，GTP 环化酶，其催化表达的第一步， 调节辅因子，四氢生物蝶呤。四氢生物蝶呤。 四氢生物蝶呤是调节 儿茶酚胺和血清素。在人类中，导致GTP缺失的突变 环化水解酶活性的特征在于不能合成这些 神经递质，导致过早死亡。在哺乳动物中也有作用 暗示这种辅因子在细胞信号传导的调节相互作用中 免疫系统和神经细胞的运作。这些角色似乎是 血清、尿液和血液中蝶啶含量极高的基础 患有HIV相关疾病的患者的脑脊液 神经系统症状和多种增殖性疾病。我们的工作 揭示了果蝇和哺乳动物的强烈同源功能， 哺乳动物和哺乳动物之间的高度保守性 果蝇GTP环化水解酶。据估计， 果蝇中的其他成分， 调节相互作用涉及神经过程， 将导致更好地了解这一重要的 神经发育的特征。

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.