Journal Article

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

O’Donnell, Michael P., Sengupta, Piali, Chao, Pin-Hao, Kammenga, Jan E.

2018

Overview

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

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptation, Physiological - genetics / Animals / Animals, Genetically Modified / Behavioral plasticity / Biology / Biology and Life Sciences / Brain - cytology / Brain - metabolism / Caenorhabditis elegans / Caenorhabditis elegans - embryology / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - physiology / Cellular stress response / Chemical communication / CRISPR / Decision making / Diet / Digestive system / Digestive tract / EPS / Feeding / Food / Food quality / Foraging behavior / Gastrointestinal tract / Gene expression / Gene Expression Regulation, Developmental / Genetic aspects / Genetic diversity / Genomes / Genomics / Growth factors / Information processing / Insulin / Intestinal Mucosa - metabolism / Intestine / Intestines / Intestines - cytology / Intestines - innervation / Laboratorium voor Nematologie / Laboratory of Nematology / Mechanistic Target of Rapamycin Complex 2 - physiology / Medicine and Health Sciences / Metabolism / Metabolites / Mitochondrial DNA / Nematodes / Nervous system / Neuroendocrine system / Neuromodulation / Neuronal Plasticity - genetics / PE&RC / Phenotype / Phenotypic plasticity / Pheromones / Physiological aspects / Quantitative trait loci / Rapamycin / Rapamycin-Insensitive Companion of mTOR Protein - physiology / Research and Analysis Methods / Sensory neurons / Sensory Receptor Cells - physiology / Signal Transduction - genetics / Temperature / TOR protein / Worms