Control of cell polarity in the C. elegans zygote

线虫受精卵细胞极性的控制

• 批准号: 6909019
• 负责人: GERALDINE Catherine Joelle SEYDOUX
• 金额: $ 23.26万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6909019
• 关键词: Caenorhabditis elegans; cellular polarity; cytoskeletal proteins; developmental genetics; functional /structural genomics; gene expression; genetic mapping; green fluorescent proteins; invertebrate embryology; larva; microfilaments; microtubules; polymerization; temperature sensitive mutant

DESCRIPTION: (provided by applicant): The long-term goal of this project is to elucidate the mechanisms that control cell polarity using the C. elegans 1-cell embryo (zygote) as model system. C. elegans offers two key advantages for this work: 1) the ability to visualize specific protein components of the polarity machinery in live cells, and 2) the ability to rapidly identify genes required for polarity using both forward and reverse genetic approaches. Establishment of the anterior-posterior (AlP) body axis of C. elegans depends on polarization of the zygote shortly after fertilization. The relevance of this system to other polarized cells was firmly established last year, when homologues of the core components of the C. elegans A/P polarity machinery were discovered in Drosophila and mammals, and shown to have similar polarity functions. Recently, we demonstrated that A/P polarity in the C. elegans zygote is triggered by microtubules emanating from the sperm asters; earlier studies also indicated a role for the actin cytoskeleton. The goal of this proposal is to identify the molecular mechanisms that link the core A/P polarity machinery to the microtubule and actin cytoskeletons. To this end, we have developed a method to monitor the establishment of A/P polarity directly in live zygotes. We will use this method to characterize the dynamics of AfP polarity, and to identify new genes involved in this process. Our screening strategy will use a functional genomics approach as well as standard genetic methods. In a pilot screen, we identified a new gene, porn-I, required for maintenance of the polarity axis during mitosis and alignment of the spindle along that axis. POM-1 is related to Pomip, a protein kinase required for polarized growth and cell division in S. pombe. Our initial findings with porn-i reveal the existence of a previously unrecognized link between spindle alignment and the A/P polarity machinery in the zygote. Cell polarity is at the core of many essential processes in animals including asymmetric cell divisions, the functioning of polarized cell types (e.g. neurons and epithelial cells), and inhibition of unregulated cell proliferation. We anticipate that our studies will provide significant insights into these processes by taking advantage of the experimental attributes of a simple model system.

描述：（由申请人提供）：该项目的长期目标是 使用秀丽隐杆线虫 1 细胞阐明控制细胞极性的机制 胚胎（受精卵）作为模型系统。线虫为此提供了两个关键优势 工作：1）能够可视化极性的特定蛋白质成分 活细胞中的机器，以及 2) 快速识别所需基因的能力 使用正向和反向遗传方法来确定极性。设立 of the anterior-posterior (AlP) body axis of C. elegans depends on polarization 受精后不久的受精卵。本系统的相关性 其他极化细胞去年牢固建立，当时 线虫 A/P 极性机制的核心部件被发现于 果蝇和哺乳动物，并显示出具有相似的极性功能。最近， 我们证明了线虫受精卵中的 A/P 极性是由 从精子紫苑发出的微管；早期的研究还表明 肌动蛋白细胞骨架的作用。该提案的目标是确定 将核心 A/P 极性机制与 microtubule and actin cytoskeletons.为此，我们开发了一种方法 直接监测活受精卵中 A/P 极性的建立。我们将使用 this method to characterize the dynamics of AfP polarity, and to identify new 参与这个过程的基因。 Our screening strategy will use a functional 基因组学方法以及标准遗传学方法。在试点屏幕中，我们 鉴定出维持极性轴所需的新基因porn-I during mitosis and alignment of the spindle along that axis. POM-1相关 Pomip，一种极化生长和细胞分裂所需的蛋白激酶 粟酒裂殖酵母。我们对色情的初步发现-我揭示了以前的存在 主轴对准和 A/P 极性机械之间未识别的联系 受精卵。细胞极性是动物许多重要过程的核心 including asymmetric cell divisions, the functioning of polarized cell types （例如神经元和上皮细胞），以及抑制不受调节的细胞 增殖。我们预计我们的研究将提供重要的见解 into these processes by taking advantage of the experimental attributes of a 简单的模型系统。