CONTROL OF CELL POLARITY IN C ELEGANS

线虫细胞极性的控制

• 批准号: 2385164
• 负责人: MICHAEL A HERMAN
• 金额: $ 9.58万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2385164
• 关键词: Caenorhabditis elegans; alleles; biological signal transduction; cellular polarity; cytogenetics; developmental genetics; fluorescence microscopy; gene complementation; gene expression; gene interaction; gene mutation; genetic mapping; genetic regulation; in situ hybridization; laboratory rabbit; microorganism genetics; molecular cloning; phenotype; protein signal sequence; regulatory gene

The long range goal of the proposed research is to understand how cell polarity is controlled during metazoan development. Genes that control the cell polarity of individual cells in the nematode C. elegans will be identified and studied using genetic and molecular methods. Mutations in one such gene, lin-44, cause the polarity of certain cells in the tall to be reversed with respect to the body axis. Lin-44 encodes a WNT protein, is expressed by the skin cells at the tip of the animal's tail and functions to specify the polarity of more anterior tall cells. The Wnt gene family encode secretory glycoproteins that act as short-range signaling molecules involved in many developmental processes in many different species. The first member of the Wnt family was isolated as a proto-oncogene that when activated caused murine breast cancer. One goal of this work is to understand how a WNT signal from cells in the tip of the tail influences the polarities of the cells that receive the signal. Novel genes that interact with C. elegans WNT gene lin-44 to control cell polarity will be identified by identifying mutations that disrupt the polarities of cells whose polarities are controlled by lin-44. Preliminary genetic screens have already identified two such genes, lop-1 and lop- 2. Genetic screens will also be used to identify mutations that act to suppress the polarity defects caused by lin-44 mutations. These newly identified genes might be involved in the production and secretion of LIN-44 signal, the reception and transduction of the signal, or the execution of the polarity information carried by LIN 44. Genetic and phenotypic characterization of the two newly identified genes that function in the control of cell polarity, lop-1 and lop-2 will be performed. Molecular analysis of lop-l and lop-2 will be performed to learn what they encode and what roles they play in the control of cell polarity. LIN-44 antibodies will be generated to identify the cells that accumulate LIN-44. Comparison of the protein localization pattern with the localization of lin-44 transcripts will help to determine other cells that secrete LIN-44 as well as cells that receive LIN-44 signal. This information will be useful in the analysis of new genes that function with lin-44 to control cell polarity. Several Wnt genes, as well as genes that have been shown to be components of the WNT signal transduction pathway, have been implicated in several forms of cancer. The identification of novel genes that interact with lin-44 to control cell polarity may also provide insights to WNT signal transduction.

拟议研究的远距离目标是了解如何 细胞极性在后生动物发育过程中受到控制。基因 控制线虫C中单个细胞的细胞极性。 秀丽隐杆线将使用遗传和分子进行鉴定和研究 方法。一个这样的基因的突变lin-44导致极性 高个子中的某些细胞相对于身体逆转 轴。 LIN-44编码Wnt蛋白，由皮肤细胞表达 在动物的尾端和功能上，以指定 更高高细胞的极性。 Wnt基因家族编码 作用于短距离信号分子的分泌糖蛋白 参与许多不同物种的许多发育过程。 Wnt家族的第一个成员被隔离为原始癌基因 激活后会导致鼠乳腺癌。一个目标 工作是了解如何在细胞尖端的细胞信号 尾部影响接收的细胞的极性 信号。与秀丽隐杆线虫相互作用的新型基因Wnt Gene Lin-44 通过识别来控制细胞极性 破坏极性的细胞极性的突变 由LIN-44控制。初步的遗传筛查已经 确定了两个这样的基因，分别是LOP-1和LOP-2。遗传筛选将 也用于识别作用以抑制的突变 LIN-44突变引起的极性缺陷。这些新发现 基因可能参与LIN-44的生产和分泌 信号，信号的接收和转导，或 Lin 44携带的极性信息的执行。遗传 和两个新鉴定的基因的表型表征 该功能在控制细胞极性，LOP-1和LOP-2方面将 被执行。 LOP-L和LOP-2的分子分析将是 表演以了解他们的编码以及他们在 控制细胞极性。 LIN-44抗体将生成 识别积累LIN-44的细胞。比较 蛋白质定位模式与LIN-44的定位 成绩单将有助于确定其他分泌LIN-44的细胞 以及接收LIN-44信号的单元。这些信息将 在分析lin-44的新基因中有用 控制细胞极性。几个Wnt基因以及 已证明是Wnt信号转导的组成部分 途径与几种形式的癌症有关。这 鉴定与Lin-44相互作用以控制的新型基因 细胞极性还可以为WNT信号转导提供见解。