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: 3303121
• 负责人: STUART K KIM
• 金额: $ 16.76万
• 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/3303121
• 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.

一个很好的模型系统，以研究遗传控制的 在线虫C中，发育是外阴的形成。优雅的 这 一个简单的发育系统可以在单细胞水平上进行研究 (the Pn.p细胞），并且超过20个指定Pn.p细胞命运的基因具有 被基因识别。 这些基因可能代表了 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传导诱导Pn.p细胞的过程 通过分析两个基因（lin-2和lin-7）表达外阴细胞命运， 可能与lin-10密切相互作用。 我们还将继续 lin-10本身的分子分析。 这一综合办法应界定 这三个基因是如何作用来指定Pn.p细胞命运的。 而且这些 研究将扩展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测 其他外阴决定基因的突变。 与此同时，我们将通过分离， 抑制lin-2、lin-7或lin-10缺陷的突变。的遗传分析 这些基因将用于推断它们如何相互作用以控制Pn.p细胞 命运 这些抑制基因突变的影响可以立即 在分子水平上进行了检查，因为同时进行了 Lin-2、Lin-7和Lin-10。 此外，我们将分析lin-31，因为该基因参与了 产生Pn.p细胞的发育潜能（三潜能 前体细胞）以及随后的特定 细胞命运 我们将研究消除的功能后果 lin-31活性，我们将研究这两者之间的遗传相互作用。 基因和其他外阴决定基因。 我们将分离lin-31基因 以确定它在分子水平上的功能，我们将 并研究其活动是如何被监管的。 这些研究与细胞增殖的控制有关。 最 癌基因通过解除信号调节而引起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的研究 应该进一步了解这些过程，可能揭示如何 它们变得不受控制，同时也识别出可能与 致癌基因等致病基因。