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

  • Neal S
  • Takeishi A
  • O'Donnell M
  • et al.
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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.Living organisms have the remarkable ability to adapt to changes in their external environment. For example, when conditions are favorable, the larvae of the tiny roundworm C. elegans rapidly mature into adults and reproduce. However, when faced with starvation, over-crowding or other adverse conditions, they can stop growing and enter a type of stasis called the dauer stage, which enables them to survive in harsh conditions for extended periods of time. The worms enter the dauer stage if they detect high levels of a pheromone mixture that is produced by other worms—which indicates that the local population is over-crowded. However, temperature, food availability, and other environmental cues also influence this decision.A protein called TGF-β and other proteins called insulin-like peptides are produced by a group of sensory neurons in the worm's head. These proteins usually promote the growth of the worms by increasing the production of particular steroid hormones. However, high levels of the pheromone mixture, an inadequate supply of food and other adverse conditions decrease the expression of the genes that encode these proteins, which allows the worm to enter the dauer state. It is not clear how the worm senses food, nor how this is integrated with the information provided by the pheromones to influence this decision.To address these questions, Neal et al. studied a variety of mutant worms that lacked proteins involved in different aspects of food sensing. The experiments show that worms missing a protein called CaMKI enter the dauer state even under conditions in which food is plentiful and normal worms continue to grow. CaMKI inhibits entry into the dauer stage by increasing the expression of the genes that encode TGF-β and the insulin-like peptides in sensory neurons in response to food.Neal et al.'s findings reveal how CaMKI enables information about food availability to be integrated with other environmental cues to influence whether young worms enter the dauer state. Understanding how food sensing is linked to changes in hormone levels will help us appreciate why and how the availability of food has complex effects on animal biology and behavior.




Neal, S. J., Takeishi, A., O’Donnell, M. P., Park, J., Hong, M., Butcher, R. A., … Sengupta, P. (2015). Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling. ELife, 4. https://doi.org/10.7554/elife.10110

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