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