Hydrogen peroxide (H2O2) controls axon pathfinding during zebrafish development

Abstract

a b s t r a c tIt 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.

Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress

“…Cell proliferation subsequent to amputation of the tail of tadpoles involves increases in H 2 O 2 concentration, as indicated by the HyPer probe (assuming that pH effects do not contribute significantly to the signal) [95]. The transients in H 2 O 2 are embedded in concerted action with other signals in the process of wound responses mentioned in the Introduction above [96]·H 2 O 2 controls axon pathfinding of retinal ganglion cells projecting towards the tectum in zebrafish [97].…”

Image-Based Measurement of H 2 O 2 Reaction-Diffusion in Wounded Zebrafish Larvae

“…H 2 O 2 is a diffusible and relatively stable reactive oxygen species that may act as an early, paracrine wound signal during tissue inflammation and regeneration (1)(2)(3)(4)(5)(6)(7)(8). Tail fin tip amputation of larval zebrafish generates a tissue-scale gradient of H 2 O 2 through Ca 2þ -dependent activation of the epithelial NADPH oxidase Duox.…”

Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity

“…It must be noted that the concentration range (50 µM to 1 mM H 2 O 2 ) that we used in vivo might seem un-physiological if directly applied to cells, however, the actual concentration that reaches the internal organs of the zebrafish larvae in vivo is likely much lower 20, 21 . To directly test if lower levels of H 2 O 2 levels can promote proliferation when applied directly to mammalian beta-cells, we treated INS-1 cells for five days with low, nontoxic levels of exogenously added H 2 O 2 or with the reducing agent N-acetyl-cysteine (NAC) as a negative control.…”