Cellular memory of developmental history in C elegans

线虫发育史的细胞记忆

基本信息

批准号：
7621033
负责人：
SARAH E HALL
金额：
$ 0.77万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2009-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The environmental and developmental experience of an animal can result in epigenetic programming of gene expression, resulting in altered behaviors and physiology. C. elegans provides a simple system in which to investigate the molecular mechanisms underlying long-term plasticity in gene expression. During the first larval stage, exposure to adverse environmental cues triggers a critical developmental decision between entry into the alternative dauer stage, or continued reproductive growth. Animals exit the dauer stage and resume reproductive growth under improved environmental conditions. A few previous reports have suggested that gene expression patterns and tissue morphology may differ between post-dauer animals and those that have bypassed the dauer stage, suggesting retention of a cellular memory of the animal's developmental and environmental history. However, the mechanisms of this cellular memory and its consequences have not been explored. Expression of the gfp reporter gene driven by the osm-9 TRPV channel gene regulatory sequences is altered in neurons of adult animals that have passed through the dauer stage, serving as an excellent marker to explore the mechanisms underlying this form of cellular memory. My goal is to identify and investigate the molecular mechanisms by which neuronal gene expression is altered by an animal's developmental and environmental experience, and to explore its behavioral and physiological consequences. Specifically, I will: 1) Explore the mechanisms by which developmental experience in larval stages regulates the expression of genes such as the osm-9 TRPV channel in adult animals, 2) Identify additional genes that are regulated by similar mechanisms, and 3) Identify the molecular pathways required for this epigenetic programming of gene expression. This work will identify the mechanisms and targets of cellular memory in C. elegans. Epigenetic programming has been described in numerous species, including mammals, and has been shown to play a critical role in differentiation and disease. The molecular mechanisms of epigenetic regulation are highly conserved across species; thus, understanding this mechanism of gene expression will be highly relevant to human development and disease. Lay summary: The goal is to understand the mechanisms of gene regulation resulting from an organism's prior developmental and environmental experience. The results of this work will allow greater understanding of the importance of early experience in long-term changes in behavior and physiology.

描述（由申请人提供）：动物的环境和发育经验会导致基因表达的表观遗传编程，从而改变行为和生理学。秀丽隐杆线虫提供了一个简单的系统，可以在其中研究基因表达中长期可塑性的分子机制。在第一个幼虫阶段，暴露于不利的环境线索会触发进入替代阶段或持续生殖生长之间的关键发展决策。在改善环境条件下，动物退出了道路阶段并恢复生殖生长。先前的一些报道表明，在dauer后动物和绕过Dauer阶段的动物之间的基因表达模式和组织形态可能会有所不同，这表明保留了动物发育和环境史的细胞记忆。但是，尚未探索这种细胞记忆及其后果的机制。 OSM-9 TRPV通道基因调节序列驱动的GFP报告基因的表达改变了经过Dauer阶段的成年动物的神经元，这是探索这种形式的细胞记忆的基础机制的绝佳标志。我的目标是识别和研究动物的发育和环境经验改变神经元基因表达的分子机制，并探索其行为和生理后果。具体而言，我将：1）探索幼虫阶段的发育经验调节基因的表达，例如成年动物中的OSM-9 TRPV通道的表达，2）确定其他受相似机制调节的基因，以及3）识别这种基因表达表达这种表性编程所需的分子途径。这项工作将确定秀丽隐杆线虫中细胞记忆的机理和靶标。表观遗传编程已在包括哺乳动物在内的许多物种中描述，并已被证明在分化和疾病中起着至关重要的作用。表观遗传调节的分子机制在物种之间高度保守。因此，了解这种基因表达机制将与人类的发育和疾病高度相关。摘要：目的是了解生物体先前的发育和环境经验产生的基因调节的机制。这项工作的结果将使人们对早期经验在行为和生理学的长期变化中的重要性。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways.

发育编程通过内源性 RNAi 途径调节线虫的嗅觉行为。

DOI：
10.7554/elife.11642
发表时间：
2016
期刊：
eLife
影响因子：
7.7
作者：
Sims,JennieR;Ow,MariaC;Nishiguchi,MailynA;Kim,Kyuhyung;Sengupta,Piali;Hall,SarahE
通讯作者：
Hall,SarahE