GENETIC CONTROL OF MICROTUBULE FUNCTION IN DEVELOPMENT

发育中微管功能的遗传控制

• 批准号: 2197354
• 负责人: ELIZABETH C. RAFF
• 金额: $ 25.05万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2197354
• 关键词: Drosophilidae; cell type; cytogenetics; developmental genetics; gene expression; gene interaction; gene mutation; genetic manipulation; genetic mapping; genetic promoter element; germ cells; histogenesis; in situ hybridization; laboratory mouse; laboratory rabbit; microtubule associated protein; microtubules; molecular cloning; nucleic acid sequence; oogenesis; protein biosynthesis; protein structure function; temperature sensitive mutant; tissue /cell culture; tubulin

The overall question which this research addresses is how the information encoded in linear form in the genome is utilized to achieve functional three-dimensional cellular substructure. The proposed research utilizes a molecular and genetic analysis of microtubule function in Drosophila. Microtubules are ubiquitous eukaryotic organelles required for many cellular processes, including cell division, mediation of cell shape, and motility of cilia and flagella. The basic unit in microtubule assembly is the alpha, beta tubulin heterodimer. Higher eukaryotes express multiple tubulin isoforms which are distinct but related proteins encoded in small multi-gene families. In addition, other proteins, collectively termed microtubule-associated proteins, are required for specific microtubule arrays. Thus, each microtubule-based structure is unique in architecture, mode of function, and total spectrum of constitutent proteins. This research addresses the nature of the genetic controls which govern how cells utilize one organelle, the microtubule, to form many morphologically and functionally distinct structures. The proposed experiments constitute genetic, biochemical, and molecular analysis of the function of Drosophila beta-tubulins during development, in differentiation of adult tissues, and in gametogenesis. The specific goals are: [1]Definition of the relationship between beta-tubulin structure and function using genetic analysis of multiple microtubule functions in the male germ line as a model system. Specific beta tubulin mutations and hybrid beta tubulin genes will be constructed and introduced into the genome in order to examine the function of particular beta tubulin domains and to test the hypothesis that divergent beta-tubulin isoforms have restricted or specialized properties. [2]Genetic, molecular, and developmental analysis of two divergent developmentally-regulated beta tubulin isoforms, beta3-tubulin and beta4-tubulin, to determine their specific roles in each of the cell types in which they are expressed.

这项研究解决的总体问题是 基因组中以线性形式编码的信息用于实现 功能性三维细胞子结构。 提议 研究利用微管的分子和遗传分析 果蝇的功能。 微管是普遍存在的真核 许多细胞过程所需的细胞器，包括细胞 纤毛和鞭毛的细胞形状介导，介导。 微管组件中的基本单元是α，β微管蛋白 异二聚体。 较高的真核生物表达多种微管蛋白同工型 是不同但相关的蛋白质，编码在小型多基因家族中。 另外，其他蛋白质共同称为微管相关 蛋白质是特定微管阵列所需的。 因此，每个 基于微管的结构在体系结构，功能模式中是独特的， 和组成蛋白的总光谱。 这项研究解决了 遗传控制的性质，该控制控制细胞如何利用一个 微管细胞器，形成许多形态和形成 功能上不同的结构。 提出的实验构成了遗传，生化和分子 分析果蝇在发育过程中的β-微管蛋白的功能， 在成年组织的分化和配子发生中。 具体 目标是：[1]β-微管蛋白之间关系的定义 使用多个微管的遗传分析结构和功能 作为模型系统的男性生殖系中的功能。 特定的beta 小管蛋白突变和杂化β微管蛋白基因将被构造，并 引入基因组，以检查 特定的β小管蛋白结构域，并检验以下假设。 发散的β-微管蛋白同工型具有限制或专业化 特性。 [2]两个的遗传，分子和发育分析 发育发育不断调节的β微管蛋白同工型，β3微管蛋白 和β4-微管蛋白，以确定它们在每个细胞中的特定作用 表达它们的类型。