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, 4, 5, 6, 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, 9, 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.

人口密度可以调节秀丽隐杆线虫的发育轨迹幼虫通过促进进入多尔滞育期，其特征是代谢和解剖重塑以及抗逆性 [1, 2]。dauer 形成的遗传分析已经确定了进化上保守的内分泌信号通路的参与，包括 DAF-2/胰岛素样受体信号通路 [3, 4, 5, 6, 7]。dauer 诱导信息素的化学和代谢组学分析确定了一个小分子家族，蛔苷，它们有效地传达增加的种群密度并促进 dauer 形成 [1, 8, 9, 10]。在这里，我们表明成年动物通过增加繁殖持续时间对在人口密度增加的条件下产生的蛔苷做出反应。我们观察到，促进幼虫进入 dauer 的蛔苷也作用于成年动物，以减弱来自 ASI 化学感应神经元的胰岛素肽 INS-6 的表达，导致神经内分泌胰岛素信号减弱，从而延长繁殖持续时间。遗传分析ins-6和相应的胰岛素信号通路突变体表明，通过典型 DAF-2-DAF-16 通路对繁殖持续时间产生影响的ins-6功能丧失模拟了种群密度增加对繁殖跨度的影响。我们进一步观察到，人口密度对生殖跨度的影响通过 DAF-12 上游的 DAF-16 依赖和 DAF-16 独立途径起作用，与在成虫中观察到的幼虫 dauer 发育决定相似。我们的数据表明，在人口密度增加的条件下，秀丽隐杆线虫动物延长了生殖产卵的持续时间，这可能使后代在更有利的条件下发育。