[Molecular cell biology on morphogenesis of the fovea and evolution of the central vision]

Since Charles Darwin wrote "On the Origin of Species by Means of Natural Selection", it had been assumed that various eye types, from the compound eye to the camera eye, had originated independently in at least 40-60 different phyletic lines. However, the finding of Pax 6, the master control gene for eye morphogenesis, and the fact that its sequence is highly conserved throughout the animal kingdom indicated that the prototype eye in a primitive animal originated only once in evolution, and various eye types arose from the same origin. We recently found a Pax 6 mutation in a pedigree with foveal hypoplasia. Thus, the Pax 6 that appeared in light sensory cells of a primitive animal in ancient times may play a role in morphogenesis of the fovea, the most highly developed visual receptor. The fovea first appeared in evolution in the temporal retina of fishes. Then, in birds, the nasal fovea and bifoveal system with nasal and temporal foveas developed. The fovea disappeared in primitive mammals, and reappeared in primates. A residue of the fovea is conserved in the visual streak, and the disappearance and reappearance of the fovea, in primitive mammals and primates respectively, correlates with degeneration and restoration of cone pigment genes in photoreceptors. Humans inherited the temporal fovea that had first originated in fish eyes. Pax 6 is expressed in the entire eyeball at an early stage of development, and is also expressed widely in the retina to determine its differentiation. To determine the position of the fovea, retinal cells are abundant in the visual streak, probably because expression of Pax 6 is regulated by patterning of the dorsoventral axis of the eyeball. Signaling molecules, discharged from the front of the face, also regulate Pax 6 expression, and determine position of the fovea, visual axis, angle gamma, growth of the eyeball, and shape of the visual field. Further investigation of nerve pathfinding system from the fovea to the central nervous system will clarify the origin of the central vision, and contribute to human welfare.