AbstractEye number varies dramatically across the animal kingdom. We recently discovered a self‐organizing gene network involving eye master control gene Pax6, which casts new light on eye number regulation. In amniote vertebrates, eye number variation manifests as cyclopia – the formation of a single eye in the centre of the head – caused by defects in midline Sonic hedgehog (Shh) signalling. In the developing embryo, the retinas derive from the optic vesicles of the primitive forebrain. Yet how the optic vesicles are themselves generated in amniote embryos, and the molecular pathways that regulate their morphogenesis, is a surprisingly neglected question. During healthy development a pair of vesicles grow either side of the anterior neural tube, contributing cells to the developing forebrain and retinas. In cyclopia a single vesicle grows at the ventral midline, which is widely attributed to a loss of Pax6 inhibition by Shh, yet paradoxically Pax6 is thought not to initiate optic vesicle outgrowth in amniotes. How then is optic vesicle outgrowth initiated and number regulated? Using chick as an experimental model, our recent data suggest that optic vesicles may normally grow from paired growth zones within the anterior neural folds of the amniote neural tube. We hypothesize that cyclopia occurs following ventral fusion of these growth zones in the absence of midline Shh signalling.