Nerves, H₂O₂ and Shh: Three players in the game of regeneration

The tight control of reactive oxygen species (ROS) levels is required during regeneration. H₂O₂ in particular assumes clear signalling functions at different steps in this process. Injured nerves induce high levels of H₂O₂ through the activation of the Hedgehog (Shh) pathway, providing an environment that promotes cell plasticity, progenitor recruitment and blastema formation. In turn, high H₂O₂ levels contribute to growing axon attraction. Once re-innervation is completed, nerves subsequently downregulate H₂O₂ levels to their original state. A similar regulatory loop between H₂O₂ levels and nerves also exists during development. This suggests that redox signalling is a major actor in cell plasticity.