Chopra Kunal, Folkmanaitė Milda, Stockdale Liam, Shathish Vishali, Ishibashi Shoko, Bergin Rachel, Amich Jorge, Amaya Enrique
Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK.
Manchester Fungal Infection Group (MFIG), Division of Evolution, Infection, and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK.
iScience. 2023 Feb 4;26(3):106147. doi: 10.1016/j.isci.2023.106147. eCollection 2023 Mar 17.
Sustained elevated levels of reactive oxygen species (ROS) have been shown to be essential for regeneration in many organisms. This has been shown primarily via the use of pharmacological inhibitors targeting the family of NADPH oxidases (NOXes). To identify the specific NOXes involved in ROS production during adult caudal fin regeneration in zebrafish, we generated mutants for , and (a key subunit of NOXes 1-4) and crossed these lines with a transgenic line ubiquitously expressing , which permits the measurement of ROS levels. Homozygous mutants had the greatest effect on ROS levels and rate of fin regeneration among the single mutants. However, : double mutants showed a greater effect on fin regeneration than the single mutants, suggesting that Nox1-4 also play a role during regeneration. This work also serendipitously found that ROS levels in amputated adult zebrafish fins oscillate with a circadian rhythm.
活性氧(ROS)水平持续升高已被证明对许多生物体的再生至关重要。这主要是通过使用针对NADPH氧化酶(NOXes)家族的药理学抑制剂来证明的。为了确定斑马鱼成年尾鳍再生过程中参与ROS产生的特定NOXes,我们构建了nox1、nox2和nox4(NOXes 1 - 4的关键亚基)的突变体,并将这些品系与一个普遍表达gfp的转基因品系杂交,从而能够测量ROS水平。在单突变体中,纯合nox4突变体对ROS水平和鳍再生速率的影响最大。然而,令人惊讶的是:双突变体对鳍再生的影响比单nox4突变体更大,这表明Nox1 - 4在再生过程中也发挥作用。这项工作还意外地发现,成年斑马鱼截肢鳍中的ROS水平以昼夜节律振荡。