Population Density Modulates the Duration of Reproduction of C. elegans

Population density can modulate the developmental trajectory of Caenorhabditis elegans larvae by promoting entry into dauer diapause, which is characterized by metabolic and anatomical remodeling and stress resistance [1, 2]. Genetic analysis of dauer formation has identified the involvement of evolutionarily conserved endocrine signaling pathways, including the DAF-2/insulin-like receptor signaling pathway [3-7]. Chemical and metabolomic analysis of dauer-inducing pheromone has identified a family of small molecules, ascarosides, which act potently to communicate increased population density and promote dauer formation [1, 8-10]. Here, we show that adult animals respond to ascarosides produced under conditions of increased population density by increasing the duration of reproduction. We observe that the ascarosides that promote dauer entry of larvae also act on adult animals to attenuate expression of the insulin peptide INS-6 from the ASI chemosensory neurons, resulting in diminished neuroendocrine insulin signaling that extends the duration of reproduction. Genetic analysis of ins-6 and corresponding insulin-signaling pathway mutants showed that the effect of increased population density on reproductive span was mimicked by ins-6 loss of function that exerted effects on duration of reproduction through the canonical DAF-2-DAF-16 pathway. We further observed that the effect of population density on reproductive span acted through DAF-16-dependent and DAF-16-independent pathways upstream of DAF-12, paralleling in adults what has been observed for the dauer developmental decision of larvae. Our data suggest that, under conditions of increased population density, C. elegans animals prolong the duration of reproductive egg laying, which may enable the subsequent development of progeny under more favorable conditions.