In C. elegans, the decision to enter a developmentally arrested, 'non-aging' dauer larval stage is primarily controlled by a secreted dauer pheromone. Small-molecule components of the dauer pheromone include several ascarylose derivatives, which work synergistically with other unidentified components of the pheromone to induce dauer formation. A detailed understanding of these dauer-inducing small molecules and their mechanism of action would enable the development of chemical tools for the study of dauer formation and for the study of related processes such as development, metabolism, and aging. In this proposal, we will fully characterize the dauer pheromone by performing structure-activity studies on the ascarosides, by identifying the chemical structures of unknown pheromone components showing synergistic activity with the ascarosides, by characterizing the mechanism of action of the pheromone components using epistasis analysis, and by transcriptionally profiling C. elegans treated with the pheromone components. By elucidating how small-molecule pheromones influence C. elegans development, our research may ultimately provide insights into how environmental cues influence human development, metabolism and aging. ? ? ?
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