Cell Cycle Control in Early Drosophila Development
果蝇早期发育中的细胞周期控制
基本信息
- 批准号:6764036
- 负责人:
- 金额:$ 33.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:DNA replicationDrosophilidaeallelescell cyclecell growth regulationcyclinsdevelopmental geneticsearly embryonic stagefertilizationgene expressiongene mutationgenetic mappingguinea pigsimmunoprecipitationin situ hybridizationinvertebrate embryologymeiosismitogen activated protein kinasemolecular cloningnorthern blottingsoogenesispolymerase chain reactionprotein structure functionregulatory genewestern blottingsyeast two hybrid system
项目摘要
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,这是至关重要的
细胞生长和分裂与发育事件相协调。最近的
进步已经定义了许多本质上起作用的调节电路
控制细胞周期的转变。这使得可以构建
在此基础上阐明发育信号如何影响细胞
周期,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。果蝇是理想的模式生物
来调查这个重要问题。有机体改变了它的细胞——
在发育过程中广泛循环,可以识别突变体
细胞周期缺陷,基因组计划允许细胞周期之间的快速转变
回收突变体并分离相关蛋白质。长期来看
目标是确定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
果蝇的成熟卵母细胞在减数分裂中期 I 停滞。有一个
当卵子通过时,激活事件,与受精无关
子宫导致减数分裂的完成。施肥是
胚胎分裂启动所需的快速周期,其中 S
有丝分裂期与有丝分裂交替,不存在间隙期。这些 S-M 周期
早期胚胎发生的周期与典型的有丝分裂周期不同
转录后控制,是在共享的核分裂中发生的
细胞质,因此需要局部激活和降解
细胞周期调节剂。特别需要 PAN GU (PNG) 蛋白激酶
在 S-M 周期期间促进有丝分裂并限制 DNA 复制。它是在
与钚 (PLU) 蛋白的复合物对于调节也至关重要
这些循环。这些蛋白质与巨核的产物一起
(gnu) 基因是维持有丝分裂细胞周期蛋白足够水平所必需的。
PNG、PLU 和 GNU 控制细胞周期蛋白的机制,从而
将定义允许有丝分裂。 PNG激酶的底物是
确定了 PNG 和 PLU 的监管。在脊椎动物中
mos癌基因对于维持卵母细胞减数分裂期间的中期停滞至关重要。
果蝇 mos 候选基因已被鉴定;它在减数分裂过程中的作用
将被划定。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 S-M 胚胎周期
已确定,将进行基因筛查以回收更多
细胞周期中这些发育变化的控制基因。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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{{ truncateString('Terry L. ORR-WEAVER', 18)}}的其他基金
Producing, provisioning, and protecting the egg: Regulation of DNA replication, mRNA translation, and proteolysis for the transition from oocyte to embryo
卵子的生产、供应和保护:从卵母细胞到胚胎过渡的 DNA 复制、mRNA 翻译和蛋白水解的调节
- 批准号:
9253418 - 财政年份:2016
- 资助金额:
$ 33.82万 - 项目类别:
Producing, provisioning, and protecting the egg: Regulation of DNA replication, mRNA translation, and proteolysis for the transition from oocyte to embryo
卵子的生产、供应和保护:从卵母细胞到胚胎过渡的 DNA 复制、mRNA 翻译和蛋白水解的调节
- 批准号:
9071147 - 财政年份:2016
- 资助金额:
$ 33.82万 - 项目类别:
Differential DNA Replication in Drosophila Development
果蝇发育中的差异DNA复制
- 批准号:
8071619 - 财政年份:1999
- 资助金额:
$ 33.82万 - 项目类别:
Differential DNA Replication in Drosophila Development
果蝇发育中的差异DNA复制
- 批准号:
8466980 - 财政年份:1999
- 资助金额:
$ 33.82万 - 项目类别:
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