NEURONAL MIGRATION IN C ELEGANS

线虫的神经元迁移

• 批准号: 2270023
• 负责人: GIAN GARRIGA
• 金额: $ 8.24万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2270023
• 关键词: Caenorhabditis elegans; alleles; beta galactosidase; cell migration; chimeric proteins; complementary DNA; developmental genetics; developmental neurobiology; egg /ovum; epitope mapping; ethology; gene mutation; invertebrate embryology; laboratory mouse; molecular cloning; motor neurons; neuronal guidance; nucleic acid sequence; phenotype; polymerase chain reaction; protein structure; tissue mosaicism; transcription factor

The overall objective of the proposed research is to investigate the regulatory mechanisms that control neuronal migration. To understand this process several key questions must be answered. How do neurons decide to migrate? What defines the pathways taken by individual migrating neurons? How do neurons know that they have reached their final destinations? Our approach to these questions is a genetic/molecular analysis of genes involved in the migrations of the Caenorhabditis elegans HSN neurons, a pair of serotonergic motor neurons required for egg laying. There are five specific aims to the proposed research. (1) Our initial goal is to identify by mutation genes required for HSN migration. The proposed genetic screens are designed to identify most HSN-migration genes, including those essential for viability or fertility. (2) Since previous mutant screens indicate that there are many genes required for HSN migration, the phenotypes of the mutants will be analyzed to determine how the genes function in HSN migration. Those genes that play key roles will be given top priority. In particular, we will focus on genes required for the migrations of multiple cell types. (3) The highest priority genes will be cloned and their sequences determined. Sequence analysis may reveal the biochemical function of a gene product, which can then be tested directly. (4) For the highest priority genes, genetic mosaic analysis and gene expression studies will be used to investigate when and where these genes function. (5) The egl-43 gene plays a key role in HSN migration and contains zinc-finger motifs that are closely related to those of the mouse Evi-1 gene. Our working model is that the Egl-43 protein transcriptionally regulates other genes that function more directly in HSN migration. This model will be tested directly by determining if the Egl-43 protein is a sequence-specific DNA binding protein. These experiments could also lead to the biochemical identification of genes that Egl-43 transcriptionally regulates. This approach should lead to a detailed understanding of how a specific neuron migrates. Mutant screens should identify most of the genes required for HSN migration. Phenotypic analysis should elucidate the roles played by the genes not only in HSN migration but also in the migration and development of other cell types. Mosaic analysis and gene expression studies should identify the cell interactions that coordinate HSN migration and molecular analysis of the genes involved should reveal the nature of these interactions.

拟议研究的总体目的是调查 控制神经元迁移的调节机制。理解这一点 处理几个关键问题必须回答。神经元如何决定 迁移？是什么定义了个体迁移神经元所采取的途径？ 神经元如何知道他们已经到达了最终目的地？我们的 这些问题的方法是对基因的遗传/分子分析 参与秀丽隐杆线虫HSN神经元的迁移，一个 产卵需要一对血清素能运动神经元。有五个 拟议研究的具体目的。 （1）我们最初的目标是 通过HSN迁移所需的突变基因识别。提议 遗传筛选旨在识别大多数HSN迁移基因，即 包括那些对于生存能力或生育力所必需的。 （2）自之前 突变屏幕表明HSN需要许多基因 迁移，将分析突变体的表型，以确定如何 基因在HSN迁移中的功能。那些扮演关键角色的基因将 被赋予最高优先事项。特别是，我们将专注于所需的基因 多种细胞类型的迁移。 （3）最高优先基因将 被克隆并确定其序列。序列分析可能揭示 基因产物的生化功能，然后可以直接测试。 （4）对于最高优先基因，遗传镶嵌分析和基因 表达研究将用于研究这些基因何时何地 功能。 （5）EGL-43基因在HSN迁移和 包含与小鼠密切相关的锌指基序 EVI-1基因。 我们的工作模型是EGL-43蛋白 转录调节其他更直接在HSN中起作用的基因 迁移。该模型将直接通过确定EGL-43来直接测试 蛋白是一种序列特异性DNA结合蛋白。这些实验 还可能导致对EGL-43基因的生化鉴定 转录调节。 这种方法应导致对特定方式的详细理解 神经元迁移。突变屏幕应确定所需的大多数基因 用于HSN迁移。表型分析应阐明扮演的角色 由基因不仅在HSN迁移中，而且在迁移和 开发其他细胞类型。马赛克分析和基因表达 研究应确定坐标HSN的细胞相互作用 涉及基因的迁移和分子分析应揭示 这些相互作用的性质。