Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903, USA.
Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903, USA.
Cell Rep. 2017 Sep 5;20(10):2501-2512. doi: 10.1016/j.celrep.2017.08.053.
Adjusting to a continuously changing environment is a key feature of life. For metazoans, environmental changes include alterations in the gut microbiota, which can affect both memory and behavior. The bacteriovorous nematode Caenorhabditis elegans discriminates between pathogenic and non-pathogenic food sources, avoiding the consumption of pathogens. Here, we demonstrate the role of the intestine in regulating C. elegans avoidance to Pseudomonas aeruginosa by an insulin-like neuropeptide encoded by ins-11. The transcriptional expression of ins-11 is controlled through transcription factor hlh-30 and the p38 mitogen-activated protein kinase (MAPK) pathway. ins-11 negatively controls signal pathways in neurons that regulate aversive learning behavior. Attenuation of ins-11 increased avoidance behavior and survival on pathogenic bacteria but decreased opportunities to find a food source as well as lowered energy storage and the number of viable progeny. Our findings support a role for the intestine in avoidance and identify an advantageous role for negative feedback that allows C. elegans to actively balance noxious and favorable environments.
适应不断变化的环境是生命的一个关键特征。对于后生动物来说，环境变化包括肠道微生物群的改变，这可能会影响记忆和行为。食细菌线虫秀丽隐杆线虫能够区分致病和非致病的食物来源，避免食用病原体。在这里，我们通过由 ins-11 编码的胰岛素样神经肽证明了肠道在调节秀丽隐杆线虫对铜绿假单胞菌的回避中的作用。ins-11 的转录表达受到转录因子 hlh-30 和 p38 丝裂原活化蛋白激酶 (MAPK) 途径的控制。ins-11 负调控调节厌恶学习行为的神经元中的信号通路。减弱 ins-11 会增加对病原菌的回避行为和存活率，但会减少寻找食物源的机会，并降低能量储存和存活后代的数量。我们的发现支持肠道在回避中的作用，并确定了负反馈的有利作用，使秀丽隐杆线虫能够主动平衡有害和有利的环境。
