NITRIC OXIDE AND DROSOPHILA DEVELOPMENT

该项目的总体目标是了解一氧化氮（NO）在生物体发育中的功能。一氧化氮是一种可扩散的多功能第二信使，与动物的许多生理功能有关。近年来，NO已成为细胞增殖、细胞分化和动物发育的重要因素。我们的研究表明，NO在生物体发育过程中作为一种抗增殖剂，调节细胞增殖和分化之间的平衡，最终控制发育中的果蝇组织和器官的形状和大小。这一提议将验证一氧化氮在生物发育和形态发生过程中是细胞增殖和分化的一般调节剂的假设。我们将结合遗传和分子方法研究NO的作用机制。我们将在dNOS位点寻找突变。这些突变将为发展dNOS基因的特异性遗传病变和筛查dNOS的遗传伴侣提供起点。我们将对分离的NOS合成酶（NOS）基因在果蝇发育过程中的分子结构进行表征，并在果蝇基因组中寻找其他NOS基因。我们将阐明能够抑制NOS活性的发育调节亚型的生物学功能，并将寻找与NOS相互作用的其他基因。最近，我们已经证明NO与视网膜母细胞瘤途径相互作用以控制果蝇的眼睛发育，在这里我们建议研究NOS与细胞周期机制组成部分之间的遗传和分子相互作用。

The overall goal of this project is to understand the function of nitric oxide (NO) in organism development. NO is a diffusible multifunctional second messenger implicated in numerous physiological functions in animals. Recently NO has emerged as an important factor in cell proliferation, cell differentiation, and animal development. Our studies have shown that NO acts as an antiproliferative agent during organism development, regulating the balance between cell proliferation and differentiation, and, ultimately, controlling the shape and size of tissues and organs in the developing Drosophila. This proposal will test the hypothesis that NO is a general regulator of cell proliferation and differentiation during organism development and morphogenesis. We will combine genetic and molecular approaches to study the mechanisms of NO action. We will search for mutations in the dNOS locus. Such mutations will provide a starting point to develop specific genetic lesions in dNOS gene and to perform screens for genetic partners of dNOS. We will characterize the molecular organization of the isolated NO synthase (NOS) genes involved in Drosophila development, and we will search for other NOS gene(s) in Drosophila genome. We will elucidate the biological functions of the developmentally regulated isoforms which are capable of inhibiting NOS activity, and we will search for other genes that interact with NOS. Recently, we have demonstrated that NO interacts with the retinoblastoma pathway to control eye development in Drosophila, and here we propose to study genetic and molecular interactions between NOS and the components of the cell cycle machinery.