Control of cell polarity in the C. elegans zygote

描述：（由申请人提供）：本项目的长期目标是 阐明机制，控制细胞极性使用C。秀丽隐杆线虫1细胞 胚胎（合子）作为模型系统。C. elegans为此提供了两个关键优势 工作：1）能够可视化特定蛋白质组分的极性 活细胞中的机械，以及2）快速识别所需基因的能力 使用正向和反向遗传方法来确定极性。建立 C. elegans依赖于极化 受精后不久的受精卵。该系统的相关性， 其他极化细胞是去年牢固建立的， C.核心组件在线虫中发现了A/P极性机制， 果蝇和哺乳动物，并显示有类似的极性功能。最近， 我们证明了C中的A/P极性。秀丽隐杆线虫受精卵是由 微管从精子的紫苑发出;早期的研究也表明， 肌动蛋白细胞骨架的作用。本提案的目标是确定 将核心A/P极性机制与 微管和肌动蛋白细胞骨架。为此，我们开发了一种方法， 直接监测活合子中A/P极性的建立。我们将使用 这种方法来表征AFP极性的动态，并识别新的 参与这个过程的基因。我们的筛选策略将使用函数 基因组学方法以及标准遗传学方法。在试点屏幕中，我们 发现了一个新的基因porn-I，它是维持极性轴所必需的 在有丝分裂和纺锤体沿着该轴排列期间。POM-1相关 Pomip是一种蛋白激酶，是细胞极化生长和细胞分裂所必需的。 S.粟球。我们对porn-i的初步发现揭示了一种先前存在的 主轴对准和A/P极性机械之间的未识别联系， 受精卵细胞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 (e.g.神经元和上皮细胞），以及抑制未调节的细胞 增殖我们预计我们的研究将提供重要的见解， 通过利用一个实验的属性， 简单模型系统

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.