Mechanisms of Developmental Timing in C. Elegans

线虫的发育时间机制

• 批准号: 0426345
• 负责人: Eric Moss
• 金额: --
• 依托单位: Rowan University School of Osteopathic Medicine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0426345&HistoricalAwards=false
• 关键词: Mechanisms; Developmental; Timing; C.; Elegans

0212373MossDevelopmental timing is fundamental to all multicellular organisms. For tissues and organs to form properly, developmental events must occur in the proper succession with the appropriate synchrony. The mechanisms that explicitly govern the timing of these events are not well understood in any organism. Valuable insights, however, have come from the investigation of heterochronic genes of the nematode Caenorhabditis elegans. Dr. Moss will investigate an new and important heterochronic gene, lin-46, which helps specify the stage-appropriate fates of cells during the animal's larval development. The LIN-46 protein acts early in the developmental timing pathway, downstream of the key regulators LIN-14 and LIN-28. Proteins related to LIN-46 in plants and animals are known to mediate protein-protein interactions. Therefore, to control developmental timing LIN-46 is likely to interact with proteins that coordinate the behaviors of cells and may be regulated by LIN-14 and LIN-28.The work outlined in this proposal will address how LIN-46 governs developmental timing from two aspects. First, Dr. Moss will elucidate the molecular relationship between the lin-46 and other heterochronic genes by determining whether lin-46 expression is regulated by lin-28 and lin-14, whether they act in the same cells, and whether they are in a linear genetic pathway. Second he will characterize the interaction of LIN-46 with other proteins. He predicts that at least one other protein encoded in the C. elegans genome interacts physically with LIN-46 and is necessary for its function. He will search for other proteins that interact with LIN-46 using molecular and genetic approaches.The long-range impact of this work will be an understanding of the molecular basis of developmental timing regulation by LIN-46 and how it has evolved. What is learned about developmental timing in C. elegans may be widely applicable to other animals. The process of developmental timing is of broad biological interest because its importance in the evolution of animal form.

0212373Moss 发育时机是所有多细胞生物的基础。为了使组织和器官正确形成，发育事件必须以适当的顺序和适当的同步性发生。在任何生物体中，明确控制这些事件发生时间的机制尚不清楚。然而，有价值的见解来自对线虫秀丽隐杆线虫异时基因的研究。 Moss 博士将研究一种新的重要异时基因 lin-46，该基因有助于确定动物幼虫发育过程中细胞的阶段性命运。 LIN-46 蛋白在发育计时途径的早期发挥作用，位于关键调节因子 LIN-14 和 LIN-28 的下游。植物和动物中与 LIN-46 相关的蛋白质已知可介导蛋白质-蛋白质相互作用。因此，为了控制发育时间，LIN-46很可能与协调细胞行为的蛋白质相互作用，并可能受到LIN-14和LIN-28的调节。本提案中概述的工作将从两个方面解决LIN-46如何控制发育时间。首先，Moss 博士将通过确定 lin-46 的表达是否受 lin-28 和 lin-14 调节、它们是否在同一细胞中起作用以及它们是否处于线性遗传途径中来阐明 lin-46 与其他异时基因之间的分子关系。其次，他将描述 LIN-46 与其他蛋白质的相互作用。他预测，线虫基因组中编码的至少一种其他蛋白质与 LIN-46 发生物理相互作用，并且是其功能所必需的。他将利用分子和遗传学方法寻找与 LIN-46 相互作用的其他蛋白质。这项工作的长期影响将是了解 LIN-46 发育时序调节的分子基础及其进化方式。关于线虫发育时间的了解可能广泛适用于其他动物。发育时间过程具有广泛的生物学意义，因为它在动物形态的进化中非常重要。