GENETIC ANALYSIS OF NEMATODE CELL DIFFERENTIATION

线虫细胞分化的遗传分析

• 批准号: 6525685
• 负责人: MARTIN CHALFIE
• 金额: $ 66.77万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-08-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6525685
• 关键词: Caenorhabditis elegans; Xenopus oocyte; cell differentiation; chimeric proteins; complementary DNA; developmental genetics; developmental neurobiology; gene expression; gene mutation; genetic promoter element; genetic screening; genetic translation; mechanoreceptors; neuronal guidance; protein protein interaction; regulatory gene; touch; transcription factor; transmission electron microscopy; voltage /patch clamp; yeast two hybrid system

We wish to continue our study of genes needed for neuronal differentiation and function in the nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis of the development and activity of a set of six touch receptor neurons (the touch cells). Previous research under this grant has led to the identification of over 500 mutations that render the animal touch insensitive. These mutations define 17 genes needed for the generation, specification, maintenance, and function of the touch cells. Four of these genes and eight others that do not mutate to touch insensitivity act combinatorially in the development of the cells, allowing them to express cell-specific features and restricting their number to six. The remaining genes encode products that are needed for the function of the cells. We have developed a model in which the proteins encoded by twelve of these genes are components or modulators of the mechanosensory apparatus needed by the cells to sense touch. This is the first molecular model for a eukaryotic mechanical sense. In the upcoming grant period we wish to investigate how this combinatorial control specifies touch cell fate, uncover new touch-cell-specific genes, and test predictions of our model of mechanosensation. The specific aims of the proposal are: 1) to characterize combinatorial regulation of touch cell fate. 2) To identify and characterize new genes needed for touch cell development and function. 3) To continue the molecular genetic characterization of genes whose products are needed for mechanosensation. 4) To investigate the electrophysiological properties of a) wild-type and mutant touch cells in situ and b) touch-cell function proteins in Xenopus oocytes.

我们希望继续我们的研究所需的基因神经元的分化和功能的线虫秀丽隐杆线虫。 与过去一样，大部分研究将集中在对一组六个触觉感受神经元（触觉细胞）的发育和活动的分析上。 此前在该基金资助下进行的研究已经确定了500多种使动物触摸不敏感的突变。 这些突变定义了触觉细胞的产生、规范、维持和功能所需的17个基因。这些基因中的四个和其他八个不会突变为触摸不敏感的基因在细胞的发育中组合作用，使它们能够表达细胞特异性特征，并将它们的数量限制在六个。 其余的基因编码细胞功能所需的产物。 我们已经开发了一个模型，其中12个基因编码的蛋白质是细胞感知触觉所需的机械感觉装置的组成部分或调节剂。 这是第一个真核生物机械感觉的分子模型。 在即将到来的资助期间，我们希望研究这种组合控制如何指定触摸细胞的命运，发现新的触摸细胞特异性基因，并测试我们的机械感觉模型的预测。 该提案的具体目标是：1）表征触摸细胞命运的组合调节。 2)识别和表征触觉细胞发育和功能所需的新基因。 3)继续进行机械感觉所需产物基因的分子遗传学表征。 4)研究非洲爪蟾卵母细胞野生型和突变型触觉细胞的电生理特性以及触觉细胞功能蛋白的电生理特性。