Fister Alexandra M, Horn Adam, Lasarev Michael, Huttenlocher Anna
bioRxiv. 2024 May 3:2023.03.14.532628. doi: 10.1101/2023.03.14.532628.
Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue-scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.
上皮损伤会引发早期活性氧（ROS）信号传导，该信号传导调节感觉神经元再生和组织修复。组织损伤的初始类型如何影响感觉轴突的早期损伤信号传导和再生生长仍不清楚。此前我们报道热损伤会在斑马鱼幼体中引发不同的早期组织反应。在此，我们发现热损伤而非机械损伤会损害感觉轴突再生和功能。实时成像显示对热损伤的即时组织反应，其特征为角质形成细胞迅速依赖Arp2/3迁移，这与组织尺度的ROS产生及感觉轴突持续损伤相关。等渗处理足以限制角质形成细胞运动、在空间上限制ROS产生并挽救感觉神经元功能。这些结果表明，早期角质形成细胞动态变化在组织修复过程中调节伤口微环境中长期信号传导的时空模式。
