Cellular memory of developmental history in C elegans

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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.