Mechanisms governing polarity in Drosophila oogenesis

果蝇卵子发生中极性的控制机制

• 批准号: 6636621
• 负责人: DANIEL D KALDERON
• 金额: $ 24.01万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6636621
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell differentiation; cell population study; confocal scanning microscopy; functional /structural genomics; gene mutation; gene targeting; genetically modified animals; germ cells; immunocytochemistry; intermolecular interaction; invertebrate embryology; lethal genes; light microscopy; microtubules; molecular biology information system; molecular polarity; morphometry; oogenesis; protein kinase A; protein localization; protein structure function; reporter genes; suppressor mutations

DESCRIPTION (Applicant's Description): Our objective is to study a signal transduction process in Drosophila oogenesis that guides a re-organization of the oocyte's microtubule cytoskeleton. The resulting polarized microtubules template the subcellular distribution of asymmetrically localized mRNAs, which define the anterior-posterior axis of the oocyte, later manifest in the embryo. These studies will complement existing molecular insights that have made Drosophila the premiere model organism for understanding how polarity and pattern are generated in a multicellular eukaryote. They will also bring molecular genetic tools to bear on a fundamental aspect of cell biology that is not well understood, namely regulation of the cytoskeleton by external signals. We anticipate that the signaling mechanisms we uncover will be conserved and thus of widespread relevance to human disease. The most immediate impact on human health is likely to come from functional insights into Drosophila genes that are homologous to human genes that are mutated in heritable diseases. Our experimental approach exploits the many classical and molecular genetic technologies that have been devised to study Drosophila development, and takes full advantage of the recent accomplishments of the Drosophila Genome Project. Our major initial aim is to identify key molecules that participate in the regulation of microtubule re-organization in oogenesis. We previously demonstrated that protein kinase A (PKA) is required for this process. We will now look for mutations in other genes that enhance mild polarity defects due to partial loss of PKA activity. We will test if the genes identified by these mutations are essential for correct microtubule re-organization and define these genes molecularly using information from the Drosophila Genome Project. Some of these newly-identified mutations will then be used to perform further, more exhaustive modifier screens to identify a more complete set of relevant genes. The nature of these gene products, their subcellular localization and potential binding partners will be determined and used to formulate and test models for signal-dependent microtubule re-organization. Thus, we aim eventually to determine the nature and source of the signal presented to the oocyte, the signal transduction pathways that are activated, and how these affect the activity or localization of microtubule organizing centers and the growth or shrinkage of microtubules nucleated from those sites.

描述（申请人的描述）：我们的目标是研究一个信号 在果蝇卵子发生的转导过程中， 卵母细胞的微管细胞骨架。由此产生的极化微管 模板的亚细胞分布的不对称定位的mRNA， 定义卵母细胞的前后轴，后来在胚胎中表现出来。 这些研究将补充现有的分子见解， 果蝇是理解极性和 模式是在多细胞真核生物中产生的。他们还将带来 分子遗传学工具，以承担细胞生物学的一个基本方面， 尚不清楚，即通过外部信号调节细胞骨架。 我们预计，我们发现的信号传导机制将是保守的， 因此与人类疾病具有广泛的相关性。最直接的影响是 人类健康可能来自对果蝇基因的功能洞察 这些基因与在遗传性疾病中突变的人类基因同源。 我们的实验方法利用了许多经典和分子遗传学 这些技术已经被设计用来研究果蝇的发育， 充分利用果蝇基因组计划的最新成果。 我们最初的主要目标是确定参与免疫反应的关键分子。 卵子发生中微管重组的调节。我们之前 证明蛋白激酶A（PKA）是这一过程所必需的。我们将 现在寻找其他基因的突变，这些突变增强了由于 PKA活性的部分丧失。我们将测试这些鉴定出的基因是否 突变对于正确的微管重组至关重要， 利用果蝇基因组计划的信息， 其中一些新发现的突变将被用于进一步的研究， 更详尽的修改器屏幕，以确定更完整的相关 基因.这些基因产物的性质，它们的亚细胞定位和 将确定潜在的结合配偶体并用于配制和测试 信号依赖性微管重组模型。因此，我们旨在 最终确定呈现给用户的信号的性质和来源。 卵母细胞，被激活的信号转导途径，以及这些 影响微管组织中心的活性或定位， 从这些位点成核的微管的生长或收缩。