Nutritional Control of Developmental Programs

发育计划的营养控制

• 批准号: 0515682
• 负责人: Ann Rougvie
• 金额: $ 48万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0515682&HistoricalAwards=false
• 关键词: Nutritional; Control; Developmental; Programs

Nutritional control of developmental programsThe long term goal of the proposed research is to elucidate the mechanism(s) by which nutritional cues are linked to the initiation of developmental programs in animals. This problem is fundamental to animal development, but has received relatively little attention at the molecular level. The simplicity of C. elegans and its ease of growth and manipulation makes it an ideal system for these studies. In particular, food availability during postembryonic development is simply controlled, and the worm's transparency allows developmental responses to food to be easily monitored. The proposal focuses on dissecting two genetic pathways: 1) a daf-18-mediated signaling pathway that actively controls the initiation of postembryonic development in response to food, and 2) the heterochronic gene pathway that times certain postembryonic events and is influenced by environmental conditions, including food availability. The presence of food initiates and coordinates timing of postembryonic developmental programs in diverse tissues of the worm. If nematodes are hatched in the absence of a food source, they arrest development. Work in the Rougvie laboratory indicates that DAF-18, the worm homolog of the tumor suppressor PTEN, is required for arrest of postembryonic developmental programs under starvation conditions. Components of the daf-18-mediated nutritional response pathway will be defined by testing candidate genes for involvement and by conducting genetic screens to identify novel components. Nutritional inputs also impinge upon the heterochronic gene pathway, but the mechanism by which these external signals influence timing genes is unknown. Temporal progression of postembryonic cell fates is triggered by the accumulation of the lin-4 microRNA which subsequently acts to down-regulate target genes. In the absence of food, lin-4 expression is not activated and development does not progress. In addition, another heterochronic gene, lin-42, is extremely sensitive to environmental conditions during development; its mutant phenotype is suppressed by adverse conditions. Genes will be identified that link environmental cues to the heterochronic gene pathway via lin-4 or lin-42. Broader impacts: This project will contribute to the training of a postdoctoral fellow, graduate and undergraduate students. Emphasis will be placed on developing testable hypotheses and critical interpretation of data. Past undergraduates in the laboratory have co-authored papers, and it is anticipated that undergraduate trainees supported with award will make similar contributions while conducting their research projects.

对发展计划的营养控制拟议的研究的长期目标是阐明营养提示与动物发展计划的启动有关的机制。 这个问题是动物发育的基础，但在分子水平上的关注相对较少。 秀丽隐杆线虫的简单性及其易于生长和操纵使其成为这些研究的理想系统。 特别是，简单地控制了胚胎后开发过程中的食物，蠕虫的透明度可以轻松监测对食物的发育反应。 该提案的重点是剖析两种遗传途径：1）DAF-18介导的信号传导途径，该途径积极控制对食物后胚胎后发育的启动，以及2）杂色基因途径，该途径在某些embryonic事件中时，并受到环境条件的影响，包括食品可用性。 食物的存在并协调了蠕虫各种组织中胚胎后发育计划的时间。 如果在没有食物来源的情况下孵化线虫，它们会阻止发展。 Rougvie实验室的工作表明，在饥饿条件下逮捕胚胎后发育计划所必需的DAF-18是肿瘤抑制剂PTEN的蠕虫同源物。 DAF-18介导的营养反应途径的成分将通过测试候选基因参与和进行遗传筛选以鉴定新成分来定义。 营养输入也影响了异缘基因途径，但是这些外部信号影响正时基因的机制尚不清楚。 Lin-4 microRNA的积累触发了胚胎细胞命运的时间进展，后来起作用靶基因。 在没有食物的情况下，LIN-4表达不会被激活，并且发育不会进展。 此外，另一个异缘基因LIN-42对发育过程中的环境条件非常敏感。它的突变表型被不利条件抑制。 将确定通过LIN-4或LIN-42将环境线索与异缘基因途径联系起来。 更广泛的影响：该项目将有助于培训博士后研究生，研究生和本科生。 将重点放在开发可检验的假设和对数据的批判性解释上。 实验室的过去的本科生共同撰写了论文，预计获得奖励的本科学员将在进行研究项目时做出类似的贡献。