Milovanovic Mina, Novkovic Mirjana, Boskovic Srdjan, Juez Rubén Marín, Milicevic Andjela, Jasnic Jovana, Milosevic Emilija, Ilic Bojan, Stainier Didier Y R, Kojic Snezana
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundora, Victoria, Australia.
Am J Physiol Cell Physiol. 2025 Jul 1;329(1):C213-C234. doi: 10.1152/ajpcell.00807.2024. Epub 2025 Jun 4.
Like mammals, zebrafish repair skeletal muscle through a multistep process that involves satellite cell activation, differentiation of progenitor cells into myocytes, their fusion into myotubes, followed by myotube maturation and myofiber hypertrophy. Coordination and timely regulation of these events are essential for functional muscle recovery. Here, we identify , a gene responsive to muscle stress, as a new player in the repair of adult zebrafish skeletal muscle and show its involvement in modulating molecular mechanisms behind myogenic cell differentiation. It is expressed in newly forming muscle fibers from the stage of myoblast-like cells to their differentiation into mature myofibers, as well as in the apparently intact muscle fibers that surround the injury. Loss of function alters regulatory pathways involved in muscle cell differentiation, contraction, and myocyte fusion, leading to the acceleration of myogenic differentiation. Our data point to as a novel marker of newly forming myofibers and a hallmark of the adaptive process occurring in the intact myofibers that are in contact with wounded tissue. Without affecting the main regulatory networks, fine-tunes skeletal muscle repair by preventing premature myogenic differentiation during injury repair, which itself could impair functional recovery. This study identifies as a novel modulator of skeletal muscle repair in adult zebrafish. Revealing its dual role in newly forming and intact myofibers near injury, the work highlights 's function in fine-tuning myogenic differentiation during repair. We position as both a marker of myofibers that repopulate wounded tissue and a player in coordination of adaptive responses essential for effective muscle tissue recovery.
与哺乳动物一样，斑马鱼通过一个多步骤过程修复骨骼肌，该过程包括卫星细胞激活、祖细胞分化为肌细胞、它们融合形成肌管，随后是肌管成熟和肌纤维肥大。这些事件的协调和及时调节对于功能性肌肉恢复至关重要。在这里，我们鉴定出一个对肌肉应激有反应的基因，它是成年斑马鱼骨骼肌修复中的一个新参与者，并表明它参与调节成肌细胞分化背后的分子机制。它在从成肌细胞样细胞阶段到其分化为成熟肌纤维的新形成的肌纤维中表达，也在损伤周围看似完整的肌纤维中表达。该基因功能的丧失会改变参与肌肉细胞分化、收缩和肌细胞融合的调节途径，导致成肌分化加速。我们的数据表明该基因是新形成的肌纤维的一个新标记，也是与受伤组织接触的完整肌纤维中发生的适应性过程的一个标志。在不影响主要调节网络的情况下，该基因通过防止损伤修复期间过早的成肌分化来微调骨骼肌修复，而过早的成肌分化本身可能会损害功能恢复。这项研究将该基因鉴定为成年斑马鱼骨骼肌修复的一种新型调节因子。揭示了它在损伤附近新形成和完整肌纤维中的双重作用，这项工作突出了该基因在修复过程中微调成肌分化的功能。我们将该基因定位为重新填充受伤组织的肌纤维的标记物以及协调有效肌肉组织恢复所必需的适应性反应的参与者。
