H₂O₂ and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H₂O₂ have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H₂O₂ levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H₂O₂ could participate in the patterning of the embryo. We find that perturbations of endogenous H₂O₂ levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H₂O₂ levels and taken up by cells with low H₂O₂ levels where it leads to increased H₂O₂ production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.