Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

Abstract

1Animals integrate external cues with information about internal conditions such as 2 metabolic state to execute the appropriate behavioral and developmental decisions. 3Information about food quality and quantity is assessed by the intestine and transmitted to 4 modulate neuronal functions via mechanisms that are not fully understood. The 5 conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in 6 response to cellular stressors and growth factors. Here we show that TORC2 coordinates 7 larval development and adult behaviors in response to environmental cues and feeding 8 state in the bacterivorous nematode C. elegans. During development, pheromone, 9 bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 10 insulin-like peptide in sensory neurons to promote a binary decision between 11 reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 12 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which 13 together reflect bacterial-diet dependent feeding status, thus providing a mechanism for 14 integration of food signals with external cues in the regulation of neuroendocrine gene 15 expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated 16 foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that 17 genetic variation affects food-dependent larval and adult phenotypes, and identify 18 quantitative trait loci (QTL) associated with these traits. Together, these results suggest 19 that TORC2 acts as a hub for communication of feeding state information from the gut to 20 the brain, thereby contributing to modulation of neuronal function by internal state. 21

Selection and gene flow shape niche-associated copy-number variation of pheromone receptor genes

“…Because dauer larvae are presumed to play a crucial role in the survival and dispersal of the species, it is likely that the decision to enter the dauer stage is under natural selection. Although differences in dauer development among small number of wild C. elegans strains have been described previously [10][11][12][13][14][15] , no underlying natural genetic variant has been identified yet. Here, we integrate laboratory experiments, computational genomic analyses, and field research to further our understanding of the genetic basis underlying microevolution of the pheromone-mediated developmental plasticity.…”

Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1

“…Given that lips-6 is the most upregulated gene in trx-1(null) mutants in a SKN-1 dependent manner, it is tempting to speculate that these two redox-independent functions of TRX-1 may be mechanistically linked. Indeed, bidirectional signalling between ASJ neurons and the intestine has been previously reported in other nutrient-dependent traits like cold-acclimation, L1 and dauer diapause or foraging behaviour [[48], [49], [50]]. Further support for using C. elegans as model to identify novel redox-independent functions of TRX-1 comes from the recent finding that TRX-1 mediates worm avoidance to Pseudomonas aeuroginosa by responding to nitric oxide produced by this pathogen [27].…”

Sex-specific,pdfr-1-dependent modulation of pheromone avoidance by food abundance enables flexibility inC. elegansforaging behavior

“…Our studies here indicate that daf-7 might act upstream of pdf-1 ; understanding this will be an important area of future research. Further, PDF-2 has recently been implicated in linking nutritional status information from the intestine to locomotor state [54], raising the intriguing possibility that PDF-1 and PDF-2 communicate external and internal information about nutrition, respectively, to PDFR-1.…”