Keratinocyte dynamics modulate the spatial organization of redox signaling during sensory neuron regeneration

Epithelial damage leads to early reactive oxygen species (ROS) signaling that regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory neurons 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 neuron regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid movement of keratinocytes, which was associated with tissue-scale ROS production and sustained sensory neuron damage. Osmotic regulation induced by 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 sensory neuron regeneration and tissue repair.