Cell Cycle Control in Early Drosophila Development

果蝇早期发育中的细胞周期控制

• 批准号: 6635970
• 负责人: Terry L. ORR-WEAVER
• 金额: $ 27.59万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635970
• 关键词: DNA replication; Drosophilidae; alleles; cell cycle; cell growth regulation; cyclins; developmental genetics; early embryonic stage; fertilization; gene expression; gene mutation; genetic mapping; guinea pigs; immunoprecipitation; in situ hybridization; invertebrate embryology; meiosis; mitogen activated protein kinase; molecular cloning; northern blottings; oogenesis; polymerase chain reaction; protein structure function; regulatory gene; western blottings; yeast two hybrid system

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.

描述(申请人提供)：在多细胞生物中，它是至关重要的 细胞的生长和分裂与发育事件相协调。近期 先进的技术已经定义了许多内在起作用的调节电路 来控制细胞周期的转变。这使得有可能构建 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 对发育线索的反应将对以下方面产生重大影响 了解癌症的原因。果蝇是一种理想的模式生物 来研究这个重要的问题。有机体修改它的细胞- 在发育过程中广泛循环，有可能用 细胞周期缺陷，而基因组计划允许在 恢复一个突变体并分离出负责的蛋白质。长期的 目的是确定减数分裂过程中细胞周期的调节 卵子发生、受精和胚胎发生的早期细胞周期。在……里面 果蝇成熟卵母细胞停滞在减数分裂中期I。有一个 激活事件，与受精无关，因为卵子通过 导致减数分裂完成的子宫。受精是 胚胎需要启动分裂，S在其中快速周期 间歇期与有丝分裂相间，没有间隔期。这些S-M周期 早期胚胎发育与典型有丝分裂周期的不同之处在于 受控于后文字，是发生在共享的 细胞质，因此需要局部激活和降解 细胞周期调节器。盘古(PNG)蛋白激酶是特别需要的 在S-M周期中促进有丝分裂和限制DNA复制。它很流行 与钚(PLU)蛋白的复合体，也是调节 这些循环。这些蛋白质，连同巨核的产物 (GNU)基因是维持有丝分裂周期蛋白水平所必需的。 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 确定了对PNG和PLU的管制。在脊椎动物中 在卵母细胞减数分裂过程中，MOS癌基因对维持中期停滞至关重要。 一个候选果蝇mos基因已被鉴定；它在减数分裂中的作用 都会被描绘出来。因为只有有限数量的基因调节 减数分裂细胞周期、卵子激活和S-M早期胚胎周期均有 将进行基因筛查，以恢复其他 控制细胞周期中这些发育变化的基因。