Neuronal IL-17 controls <i>Caenorhabditis elegans</i> developmental diapause through CEP-1/p53
Abhishiktha Godthi, Sehee Min, Srijit Das, Johnny Cruz-Corchado, Andrew Deonarine, Kara Misel‐Wuchter, Priya D. Issuree, Veena Prahlad
Abstract
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 Caenorhabditis 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, up-regulates 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-17 s 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.