Draper-mediated efferocytosis by Drosophila imaginal disc epithelial cells clears cellular debris during regeneration.

Article summaryTissue regeneration requires organized responses to damage, including clearance of cellular debris. Using a genetic ablation system in Drosophila wing imaginal discs, we show that most debris is cleared within two days despite the absence of immune cell recruitment, which is restricted by the basement membrane. In the absence of immune cells, debris clearance occurs through Draper-mediated efferocytosis and lysosomal processing by epithelial cells. Disruption of this pathway delays debris removal and impacts regeneration. Residual debris consists of a heterogeneous mix of cellular components, indicating non-selective clearance. Together, our findings identify epithelial cells as key non-professional phagocytes during regeneration. Regeneration is a coordinated process that restores tissue integrity following damage. Following injury, tissues initiate early responses, including epithelial remodeling and clearance of cellular debris. However, how debris clearance is coordinated with regenerative growth to ensure efficient tissue repair remains poorly understood. To address how early damage responses, particularly debris clearance, are coordinated with regeneration, we used a genetic ablation system in Drosophila wing imaginal discs to induce apoptosis in the pouch region. Targeted damage generates cellular debris that localizes to both the apical and basal sides of the epithelium. We show that most cellular debris is cleared within two days after damage, although some debris persists apical to the regenerating epithelium. Notably, immune cells are not recruited to the damaged tissue due to restricted access by an intact basement membrane. Instead, we discovered that debris clearance is mediated by efferocytosis, whereby neighboring hinge epithelial cells activate JNK signaling and engulf debris via lysosomal formation. Reduction of efferocytosis by mutation of the phagocytic receptor Draper delays debris removal and increases debris persistence. This impairment has a modest impact on regeneration, as measured by adult wing size. Finally, our data indicate that residual debris consists of a heterogeneous mixture of cellular components, suggesting no preferential targeting by the clearance machinery. Together, our results reveal a previously unappreciated role for epithelial cells as non-professional phagocytes for debris clearance during regeneration.