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