Cell Cycle Control in Early Drosophila Development

果蝇早期发育中的细胞周期控制

• 批准号: 6764036
• 负责人: Terry L. ORR-WEAVER
• 金额: $ 33.82万
• 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/6764036
• 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（由申请人提供）：在多细胞生物中，至关重要 该细胞生长和分裂与发育事件协调。最近的 进步已经定义了大部分的调节电路，该电路本质上起作用 控制通过细胞周期的过渡。这使得建立可能 在这个基础上阐明发育信号如何影响细胞 循环，鉴定影响细胞增殖的调节基因 对发展线索的反应将对 了解癌症的原因。果蝇是理想的模型生物 这要调查这个重要的问题。生物体修饰其细胞 - 在开发过程中广泛循环，可以识别具有的突变体 细胞周期缺陷，基因组项目允许在 恢复突变体并隔离负责的蛋白质。长期 目的是定义减数分裂细胞周期的调节 卵子发生，受精和胚胎发生的早期细胞周期。在 果蝇成熟的卵母细胞在减数分裂的中期I中被捕。有一个 当卵通过时，激活事件与受精无关 导致减数分裂分裂的子宫。受精是 启动胚胎分裂的必需品，快速周期 相位与有丝分裂交替，而无需干预间隙阶段。这些S-M周期 早期胚胎发生与原型有丝分裂周期不同 在书面上受控，是在共享中发生的核师 细胞质，结果需要局部激活和降解 细胞周期调节剂。需要特别需要PAN GU（PNG）蛋白激酶 促进有丝分裂并限制S-M循环期间的DNA复制。它在 与p蛋白（PLU）蛋白的复合物，这对于调节也是必不可少的 这些周期。这些蛋白质以及巨型核的产物 （GNU）基因需要维持足够水平的有丝分裂细胞周期蛋白蛋白。 PNG，PLU和GNU控制细胞周期蛋白蛋白的机制，从而 允许有丝分裂定义。 PNG激酶的底物将是 确定，并确定了PNG和PLU的调节。在脊椎动物中 MOS癌基因对于在卵母细胞减数分裂过程中维持中期停滞至关重要。 已经确定了候选果蝇基因。它在减数分裂中的作用 将被描述。因为只有有限数量的基因调节 减数分裂细胞周期，卵子激活和早期的S-M胚胎周期具有 已确定，将进行遗传屏幕以恢复额外 控制细胞周期中这些发育变化的控制基因。