Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling

Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF-β and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity.