Mechanisms governing polarity in Drosophila oogenesis

果蝇卵子发生中极性的控制机制

• 批准号: 6743674
• 负责人: DANIEL D KALDERON
• 金额: $ 23.99万
• 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 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743674
• 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)：我们的目标是研究信号 果蝇卵子发生中引导重组的转导过程 卵母细胞的微管细胞骨架。由此产生的极化微管 模板非对称定位的mRNAs的亚细胞分布， 确定卵母细胞的前后轴，随后在胚胎中表现出来。 这些研究将补充现有的分子洞察力 果蝇是最好的模式生物，用于理解极性和 模式在多细胞真核生物中产生。他们还将带来 分子遗传学工具涉及细胞生物学的一个基本方面，即 没有很好地理解，即外部信号对细胞骨架的调节。 我们预计，我们发现的信号机制将被保守和 因此与人类疾病具有广泛的相关性。最直接的影响是 人类的健康很可能来自对果蝇基因的功能洞察 这些基因与在可遗传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 为研究果蝇发育而设计的技术，并采取了 充分利用果蝇基因组计划最近取得的成就。 我们的主要初始目标是确定参与该过程的关键分子 卵子发生过程中微管重组的调控。我们之前 证明了蛋白激酶A(PKA)是这一过程所必需的。我们会 现在寻找其他基因的突变，这些基因增强了由于 PKA活性部分丧失。我们将测试由这些基因识别的基因 突变对于正确的微管重组和定义是必不可少的 这些基因利用果蝇基因组计划中的信息进行分子生物学研究。 这些新发现的突变中的一些将被用来进行进一步的研究， 更详尽的修饰符屏幕，以识别更完整的相关 基因。这些基因产物的性质，它们的亚细胞定位和 将确定潜在的有约束力的合作伙伴，并将其用于制定和测试 信号依赖的微管重组模型。因此，我们的目标是 最终确定提供给 卵母细胞，被激活的信号转导通路，以及这些 影响微管组织中心的活动或定位，以及 从这些部位成核的微管的生长或收缩。

项目成果

Regulation of microtubules by Rho GTPases in migrating cells.

• DOI: 10.1002/047001766x.ch10
• 发表时间: 2005
• 期刊: Novartis Foundation symposium
• 作者: G. Gundersen;Y. Wen;Christina H. Eng;J. Schmoranzer;N. Cabrera-Poch;E. Morris;Michael Chen;E. Gomes

The RNA-binding protein Squid is required for the establishment of anteroposterior polarity in the Drosophila oocyte.

RNA 结合蛋白 Squid 是果蝇卵母细胞前后极性建立所必需的。

• DOI: 10.1242/dev.02159
• 发表时间: 2005
• 期刊: Development (Cambridge, England)
• 作者: Steinhauer,Josefa;Kalderon,Daniel
• 通讯作者: Kalderon,Daniel

The sulindac derivatives OSI-461, OSIP486823, and OSIP487703 arrest colon cancer cells in mitosis by causing microtubule depolymerization.

舒林酸衍生物 OSI-461、OSIP486823 和 OSIP487703 通过引起微管解聚来阻止结肠癌细胞有丝分裂。

• DOI: 10.1158/1535-7163.mct-05-0260
• 发表时间: 2006
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Xiao,Danhua;Deguchi,Atsuko;Gundersen,GreggG;Oehlen,Bert;Arnold,Lee;Weinstein,IBernard
• 通讯作者: Weinstein,IBernard