Hydrogen peroxide (H2O2) controls axon pathfinding during zebrafish development

Abstract It is now becoming evident that hydrogen peroxide (H 2 O 2 ), which is constantly produced by nearly all cells, contributes to bona fide physiological processes. However, little is known regarding the distribution and functions of H 2 O 2 during embryonic development. To address this question, we used a dedicated genetic sensor and revealed a highly dynamic spatio-temporal pattern of H 2 O 2 levels during zebrafish morphogenesis. The highest H 2 O 2 levels are observed during somitogenesis and organogenesis, and these levels gradually decrease in the mature tissues. Biochemical and pharmacological approaches revealed that H 2 O 2 distribution is mainly controlled by its enzymatic degradation. Here we show that H 2 O 2 is enriched in different regions of the developing brain and demonstrate that it participates to axonal guidance. Retinal ganglion cell axonal projections are impaired upon H 2 O 2 depletion and this defect is rescued by H 2 O 2 or ectopic activation of the Hedgehog pathway. We further show that ex vivo , H 2 O 2 directly modifies Hedgehog secretion. We propose that physiological levels of H 2 O 2 regulate RGCs axonal growth through the modulation of Hedgehog pathway.