Control of cell polarity in the C. elegans zygote

描述：(申请人提供)：本项目的长期目标是 阐明利用线虫1-cell控制细胞极性的机制 以胚胎(受精卵)为模型系统。线虫为此提供了两个关键优势 工作：1)显示极性的特定蛋白质成分的能力 活细胞中的机械，以及2)快速识别所需基因的能力 使用正向遗传方法和反向遗传方法的极性。编制 线虫的前-后(ALP)体轴与极化有关 受精后不久的受精卵。这一系统与 去年，其他极化细胞被牢固地建立起来，当时 线虫A/P极性机械的核心部件在 果蝇和哺乳动物，并被证明具有相似的极性功能。最近， 我们证明线虫受精卵中的A/P极性是由 从精巢发出的微管；早期的研究也表明 肌动蛋白细胞骨架的作用。这项提案的目标是确定 将核心A/P极性机制连接到 微管和肌动蛋白细胞骨架。为此，我们开发了一种方法来 直接监测活体受精卵中A/P极性的建立。我们将使用 这种方法可以用来表征AFP的极性动态，并识别新的 参与这一过程的基因。我们的筛选策略将使用功能 基因组学方法以及标准遗传方法。在飞行员屏幕上，我们 发现了维持极轴所需的新基因--Porn-I 在有丝分裂和纺锤体沿该轴排列期间。POM-1相关 对Pomip来说，这是一种蛋白激酶，在细胞的极化生长和分裂中 S.pombe。我们对色情的初步发现-我揭示了之前 主轴对中与A/P极性机械之间的未知链接 受精卵。细胞的极性是动物许多基本过程的核心 包括不对称的细胞分裂，极化细胞类型的功能 (例如，神经元和上皮细胞)和对未受调控的细胞的抑制 扩散。我们预计，我们的研究将提供重要的见解 通过利用 简单的模型系统。

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.