Neuronal IL-17 controls C. elegans developmental diapause through CEP-1/p53

摘要: During metazoan development, how cell division and metabolic programs are coordinated with nutrient availability remains unclear. Here, we show that nutrient availability signaled by the neuronal cytokine, ILC-17.1 switches C. elegans development between reproductive growth and dormancy by controlling the activity of the tumor suppressor p53 ortholog, CEP-1. Specifically, upon food availability, ILC-17.1 signaling by amphid neurons promotes glucose utilization and suppresses CEP-1/p53 to allow growth. In the absence of ILC-17.1, CEP-1/p53 is activated, upregulates cell-cycle inhibitors, decreases phosphofructokinase and cytochrome C expression, and causes larvae to arrest as stress-resistant, quiescent dauers. We propose a model whereby ILC-17.1 signaling links nutrient availability and energy metabolism to cell cycle progression through CEP-1/p53. These studies describe ancestral functions of IL-17s and the p53-family of proteins and are relevant to our understanding of neuroimmune mechanisms in cancer. They also reveal a DNA damage-independent function of CEP-1/p53 in invertebrate development and support the existence of a previously undescribed C. elegans dauer pathway.During metazoan development, nutrient availability is coordinated with the division, growth and metabolic activity of individual cells through cell-cell communication. This is also the case in the invertebrate C. elegans, a free-living bacterivore, which displays a dramatic developmental plasticity to ensure that its growth and reproduction match available resources(–). When C. elegans larvae hatch under optimal conditions (at 20°C, low population …