Cellular memory of developmental history in C elegans

线虫发育史的细胞记忆

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7621033
• 关键词: Address; Adult; Animals; Behavior; Behavioral; Bypass; Caenorhabditis elegans; Cues; Development; Disease; Epigenetic Process; Exposure to; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genomics; Goals; Growth; Human Development; Mammals; Memory; Molecular; Morphology; Neurons; Organism; Pathway interactions; Pattern; Physiological; Physiology; Play; Process; Recording of previous events; Regulation; Regulator Genes; Reporter Genes; Reporting; Role; Staging; System; TRPV channel; Tissues; Work; cellular targeting; early experience; experience; improved; mature animal; programs; reproductive

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可能导致基因表达的表观遗传编程，导致行为和生理的改变。线虫提供了一个简单的系统来研究基因表达长期可塑性的分子机制。在第一个幼虫阶段，暴露在不利的环境线索下，会引发关键的发育决定，是进入另一个幼虫阶段，还是继续生殖生长。动物退出达尔阶段，在改善的环境条件下恢复生殖生长。之前的一些报告表明，后达尔阶段的动物和那些绕过达尔阶段的动物的基因表达模式和组织形态可能不同，这表明动物的发育和环境历史保留了细胞记忆。然而，这种细胞记忆的机制及其后果还没有被探索。在经历了Dauer阶段的成年动物的神经元中，由OSM-9 TRPV通道基因调控序列驱动的GFP报告基因的表达发生了变化，这是探索这种形式细胞记忆的机制的一个很好的标记。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。具体地说，我将：1)探索幼虫阶段的发育经验调节成年动物中OSM-9 TRPV通道等基因表达的机制；2)确定受类似机制调控的其他基因；3)确定基因表达的表观遗传编程所需的分子途径。这项工作将确定线虫细胞记忆的机制和目标。表观遗传编程已在包括哺乳动物在内的许多物种中被描述，并已被证明在分化和疾病中发挥关键作用。表观遗传调控的分子机制在不同物种之间是高度保守的；因此，了解这种基因表达的机制将与人类发育和疾病高度相关。内容提要：本课程的目标是了解生物体先前的发育和环境经验导致的基因调控机制。这项工作的结果将使人们更好地理解早期经验在行为和生理长期变化中的重要性。

项目成果

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