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