title: Hydrogen peroxide (H2O2) controls axon pathfinding during zebrafish development.
abstract: It is now becoming evident that hydrogen peroxide (H2O2), which is constantly produced by nearly all cells, contributes to bona fide physiological processes. However, little is known regarding the distribution and functions of H2O2 during embryonic development. To address this question, we used a dedicated genetic sensor and revealed a highly dynamic spatio-temporal pattern of H2O2 levels during zebrafish morphogenesis. The highest H2O2 levels are observed during somitogenesis and organogenesis, and these levels gradually decrease in the mature tissues. Biochemical and pharmacological approaches revealed that H2O2 distribution is mainly controlled by its enzymatic degradation. Here we show that H2O2 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 H2O2 depletion and this defect is rescued by H2O2 or ectopic activation of the Hedgehog pathway. We further show that ex vivo, H2O2 directly modifies Hedgehog secretion. We propose that physiological levels of H2O2 regulate RGCs axonal growth through the modulation of Hedgehog pathway.
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; PSL Research University, 75005 Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Gauron
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; École Normale Supérieure, Institute of Biology at the Ecole Normale Supérieure (IBENS), CNRS UMR8197, INSERM U1024, F-75005 Paris, France; PSL Research University, 75005 Paris, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Meda
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; PSL Research University, 75005 Paris, France.
authors.forename: Edmond
authors.initials: E
authors.lastname: Dupont
authors.affiliation: Institut Curie CNRS UMR3215, INSERM U934, F-75248, France; PSL Research University, 75005 Paris, France.
authors.forename: Shahad
authors.initials: S
authors.lastname: Albadri
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; PSL Research University, 75005 Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Quenech'Du
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; École Normale Supérieure, Institute of Biology at the Ecole Normale Supérieure (IBENS), CNRS UMR8197, INSERM U1024, F-75005 Paris, France; PSL Research University, 75005 Paris, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Ipendey
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; École Normale Supérieure, Institute of Biology at the Ecole Normale Supérieure (IBENS), CNRS UMR8197, INSERM U1024, F-75005 Paris, France; PSL Research University, 75005 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Volovitch
authors.affiliation: Institut Curie CNRS UMR3215, INSERM U934, F-75248, France; PSL Research University, 75005 Paris, France.
authors.forename: Filippo
authors.initials: F
authors.lastname: Del Bene
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; PSL Research University, 75005 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Joliot
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; Université Paris Diderot, Sorbonne Paris Cité, Biology Department, 75205 Paris Cedex 13, France; PSL Research University, 75005 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rampon
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB), CNRS UMR 7241/INSERM U1050/Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France; Université Paris Diderot, Sorbonne Paris Cité, Biology Department, 75205 Paris Cedex 13, France; PSL Research University, 75005 Paris, France. Electronic address: vriz@univ-paris-diderot.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vriz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000071437:Axon Guidance / Q000187:drug effects* / Q000502:physiology; D001369:Axons / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008164:Luminescent Proteins / Q000032:analysis; D055495:Neurogenesis / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D008164:Luminescent Proteins; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003545:Cysteine
keywords: Axon pathfinding; Hedgehog; Hydrogen peroxide