Cell Cycle Control in Early Drosophila Development

描述（由申请人提供）：在多细胞生物中， 细胞的生长和分裂与发育事件相协调。最近 进步已经定义了许多内在作用的调节电路， 来控制细胞周期的转换。这使得建立 在此基础上阐明发育信号如何影响细胞 细胞周期中影响细胞增殖的调控基因的鉴定 对发展线索的反应将对 了解癌症的原因。果蝇是昆虫学中理想的模式生物 来研究这个重要的问题。有机体会改变它的细胞- 在发育过程中广泛循环，有可能识别突变体， 细胞周期缺陷，基因组计划允许快速过渡， 回收突变体并分离出负责的蛋白质长期 目的是确定减数分裂细胞周期的调控过程中， 卵子发生、受精和胚胎发生的早期细胞周期。在 果蝇的成熟卵母细胞停滞在减数分裂的中期I。有一个 激活事件，独立于受精，因为鸡蛋通过 导致减数分裂完成的子宫。施肥是 所需的启动胚胎分裂，快速周期，其中S 期与有丝分裂交替，没有间隔期。这些S-M周期 早期胚胎发生的有丝分裂周期与典型的有丝分裂周期不同， 在转录后被控制，是发生在一个共享的 细胞质，因此需要局部激活和降解 细胞周期调节剂。PAN GU（PNG）蛋白激酶是特异性需要的 促进有丝分裂并限制S-M周期中的DNA复制。符合 与钚（PLU）蛋白的复合物，也是调节 这些周期。这些蛋白质和巨核的产物 (gnu)基因，需要保持足够水平的有丝分裂细胞周期蛋白。 PNG、PLU和GNU控制细胞周期蛋白的机制， 允许有丝分裂将被定义。PNG激酶的底物将是 确定，并确定PNG和PLU的监管。在脊椎动物中， mos癌基因是维持卵母细胞减数分裂中期阻滞的关键。 一个候选果蝇mos基因已被确定;它在减数分裂中的作用 将被划定。因为只有有限数量的基因调控 减数分裂细胞周期、卵子激活和早期S-M胚胎周期 一旦确定，将进行遗传筛查，以恢复额外的 控制细胞周期中这些发育变化的基因。

DESCRIPTION (provided by applicant): In multicellular organisms it is crucial that cell growth and division be coordinated with developmental events. Recent advances have defined much of the regulatory circuitry that acts intrinsically to control transitions through the cell cycle. This makes it possible to build on this foundation to elucidate how developmental signals affect the cell cycle, Identification of regulatory genes affecting cell proliferation in response to developmental cues will have significant implications for understanding the causes of cancer. Drosophila is an ideal model organism in which to investigate this important question. The organism modifies its cell- cycle extensively during development, it is possible to identify mutants with cell cycle defects, and the genome project permits a rapid transition between recovering a mutant and isolating the responsible protein. The long-term objectives are to define the regulation of the meiotic cell cycle during oogenesis, fertilization, and the early cell cycles of embryogenesis. In Drosophila the mature oocyte is arrested at metaphase I of meiosis. There is an activation event, independent of fertilization, as the egg passes through the uterus that causes the completion of the meiotic divisions. Fertilization is required for the initiation of embryonic divisions, rapid cycles in which S phase alternates with mitosis without intervening gap phases. These S-M cycles of early embryogenesis differ from archetypical mitotic cycles in being controlled postranscriptionally, being nuclear divisions that occur in a shared cytoplasm, and as a result requiring localized activation and degradation of cell cycle regulators. The PAN GU (PNG) protein kinase is required specifically to promote mitosis and limit DNA replication during the S-M cycles. It is in complex with the PLUTONIUM (PLU) protein that is essential also to regulate these cycles. These proteins, together with the product of the giant nuclei (gnu) gene, are needed to maintain adequate levels of mitotic Cyclin proteins. The mechanism by which PNG, PLU, and GNU control Cyclin proteins and thus permit mitosis will be defined. Substrates of the PNG kinase will be identified, and the regulation of PNG and PLU determined. In vertebrates the mos oncogene is crucial to maintain metaphase arrest during meiosis in oocytes. A candidate Drosophila mos gene has been identified; its role during meiosis will be delineated. Because only a limited number of genes regulating the meiotic cell cycle, egg activation, and the early S-M embryonic cycles have been identified, a genetic screen will be carried out to recover additional control genes for these developmental changes in the cell cycle.