Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA, United States of America.
Laboratory of Nematology, Wageningen University and Research, Wageningen, The Netherlands.
PLoS Genet. 2018 Feb 7;14(2):e1007213. doi: 10.1371/journal.pgen.1007213. eCollection 2018 Feb.
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.
动物将外部线索与代谢状态等内部状况的信息整合起来，以执行适当的行为和发育决策。肠道会评估有关食物质量和数量的信息，并通过尚未完全了解的机制将其传递给神经元，以调节其功能。保守的雷帕霉素靶蛋白复合物 2（TORC2）可响应细胞应激源和生长因子来控制多种过程。在这里，我们表明 TORC2 可响应环境线索和摄食状态来协调细菌食性线虫 C. elegans 的幼虫发育和成年行为。在发育过程中，信息素、细菌食物和温度调节感觉神经元中 daf-7 TGF-β 和 daf-28 胰岛素样肽的表达，以促进生殖生长和进入替代 dauer 幼虫阶段之间的二元决策。我们发现 TORC2 在肠道中起作用，以调节 daf-7 和 daf-28 的神经元表达，这两者共同反映了细菌饮食依赖性摄食状态，从而为将食物信号与外部线索整合到神经内分泌基因表达的调节中提供了一种机制。在成年期，TORC2 同样通过 PDF-2/PDFR-1 神经肽信号依赖性途径在肠道中发挥作用，以调节食物调节的觅食行为。我们还证明了遗传变异会影响依赖食物的幼虫和成年表型，并确定了与这些特征相关的数量性状基因座（QTL）。综上所述，这些结果表明，TORC2 充当从肠道到大脑传递摄食状态信息的枢纽，从而有助于通过内部状态来调节神经元功能。
