Pins Suppresses Abnormal Cell Fate Reprogramming During Wing Regeneration in <i>Drosophila</i>

Abstract

During regeneration, cell fate reprogramming contributes to the formation of original tissue structure by integrating with the cellular requirement for tissue growth and remodeling. These regenerative responses are orchestrated by multiple signaling pathways and secreting factors, and thus they must be tightly controlled to prevent abnormal consequences. However, the mechanisms that ensure proper regenerative responses and suppress abnormal cell fate change during regeneration are poorly understood. Here, using the genetic ablation system in the Drosophila wing disc epithelium, we show that Partner of inscuteable (Pins), the vertebrate homologue of LGN/AGS3 and known regulator of mitotic spindle orientation, suppresses the notum-to-wing abnormal transformation during regeneration. Using tissue-specific genetic manipulations, we clarify that Pins in the wing pouch is responsible for impeding ectopic wing formation. We further show that disruption of Pins in the wing pouch induces ectopic regenerative responses in the notum, including activation of JNK and JAK/STAT signaling, both of which are required for the formation of the ectopic wing. After ablation, stress responses in the wing pouch are prolonged when pins is attenuated, leading to the continuous expression of secreting factors as well as defects in wing regeneration. Interestingly, Pins is not required for mitotic spindle orientation in the wing pouch or in the notum during regeneration, suggesting a novel function of Pins in the interphase epithelial cells. Taken together, these results demonstrate that Pins suppresses aberrant cell fate reprogramming by inhibiting excessive regenerative responses.