GENETIC CONTROL OF VULVAL CELL FATES IN C ELEGANS

线虫外阴细胞命运的遗传控制

• 批准号: 3303122
• 负责人: STUART K KIM
• 金额: $ 15.8万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3303122
• 关键词: Caenorhabditis elegans; biological models; biological signal transduction; cell differentiation; cell growth regulation; cytogenetics; developmental genetics; gene expression; gene mutation; genetic regulation; genetically modified animals; microinjections; micromanipulator; molecular cloning; reporter genes; suppressor mutations

An excellent model system to which to study the genetic control of development is the formation of the vulva in the nematode C. elegans. This simple developmental system can be studied at the levels of single cells (the Pn.p cells), and over twenty genes that specify Pn.p cell fate have been genetically identified. These genes may represent most of the key steps in the process of cellular determination, including signal reception, signal transduction and gene regulation. We will study the process whereby cell-cell signalling induces Pn.p cells to express vulval cell fates by analyzing two genes (lin-2 and lin-7) that are likely to interact closely with lin-10. We will also continue our molecular analysis of lin-10 itself. This combined approach should define how these three genes act to specify Pn.p cell fate. Furthermore, these studies will extend our understanding of the entire signalling pathway, because probes for these genes can be used to examine the effects of mutations in any of the other vulval determination genes. Concomitantly, we will identify new vulval determination genes by isolating mutations that suppress lin-2, lin-7 or lin-10 defects. Genetic analysis of these genes will be used to deduce how they interact to control Pn.p cell fate. The effects of these suppressor mutations can be immediately examined at the molecular level due to the concurrent molecular cloning of lin-2, lin-7 and lin-10. In addition, we will analyze lin-31 because this gene is involved in generating the developmental potential of Pn.p cells (tripotential precursor cells) as well as the subsequent specification of a particular cell fate. We will examine the functional consequences of an elimination of lin-31 activity and we will study the genetic interactions between this gene and other vulval determination genes. We will isolate the lin-31 gene in order to determine how it functions at the molecular level, and we will also examine how its activity is regulated. These studies are relevant to the control of cell proliferation. Most oncogenes cause uncontrolled cell growth by deregulating either signal transduction or gene regulation. Studies using this simple model system should further our knowledge about these processes, possibly revealing how they become deregulated and also identifying genes that may interact with disease-causing genes such as oncogenes.

一种研究遗传控制的优良模式系统 线虫的外阴发育是线虫外阴的形成。这 可以在单细胞水平上研究简单的发育系统 以及20多个决定Pn.p细胞命运的基因 已经被基因鉴定了。这些基因可能代表了大多数关键 在蜂窝确定过程中的步骤，包括信号接收， 信号转导和基因调控。 我们将研究细胞间信号诱导Pn.p细胞的过程 通过分析两个基因(Lin-2和lin-7)来表达外阴细胞的命运 很可能与林-10密切互动。我们还将继续我们的 LIN-10本身的分子分析。这种组合方法应该定义 这三个基因如何决定Pn.p细胞的命运。此外，这些 研究将扩大我们对整个信号通路的理解， 因为这些基因的探针可以用来检查 任何其他外阴决定基因的突变。 与此同时，我们将通过分离鉴定新的外阴决定基因 抑制LIN-2、LIN-7或LIN-10缺陷的突变。遗传病的分析 这些基因将被用来推断它们如何相互作用来控制Pn.p细胞 命运。这些抑制子突变的影响可以立即 由于同时进行了分子克隆，在分子水平上进行了检查 林-2、林-7和林-10。 此外，我们将分析林-31，因为这个基因参与了 产生Pn.p细胞的发育潜力(三潜能 前体细胞)以及特定的 细胞的命运。我们将研究淘汰的功能后果 LIN-31的活性，我们将研究这一基因之间的相互作用 基因和其他外阴决定基因。我们将分离出LIN-31基因 为了确定它如何在分子水平上发挥作用，我们将 还要研究它的活动是如何受到监管的。 这些研究与细胞增殖的控制有关。多数 癌基因通过解除对任一信号的调控而导致不受控制的细胞生长 转导或基因调控。使用这个简单的模型系统进行研究 应该进一步加深我们对这些过程的了解，可能会揭示 它们变得不受管制，并识别可能与 致病基因，如癌基因。