1 Aquatic vertebrates have a remarkable ability to regenerate limbs and tails after 2 amputation. Previous studies indicate that reactive oxygen species (ROS) signalling 3 initiates regeneration, but the mechanism by which this takes place is poorly 4 understood. Developmental signalling pathways have been shown to have pro-5 regenerative roles in many systems. However, whether these are playing roles that 6 are specific to regeneration, or are simply recapitulating their developmental 7 functions is unclear. We have analysed zebrafish larval tail regeneration and find 8 evidence that ROS released upon wounding cause repositioning of notochord cells to 9 the damage site. These cells secrete Hedgehog ligands which are required for 1 0 regeneration. Hedgehog signalling is not required for normal tail development 1 1 suggesting that it has a regeneration specific role. Our results provide a model for 1 2 how ROS initiate tail regeneration, and indicate that developmental signalling 1 3 pathways can play regenerative functions that are not directly related to their 1 4 developmental roles.
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