Fgf8 Expression and Degradation of Retinoic Acid Are Required for Patterning a High-Acuity Area in the Retina

Species that are highly reliant on their visual system have a specialized retinal area subserving high-acuity vision, e.g., the fovea in humans. Although of critical importance for our daily activities, little is known about the mechanisms driving the development of retinal high-acuity areas (HAAs). Using the chick as a model, we found a precise and dynamic expression pattern of fibroblast growth factor 8 (Fgf8) in the HAA anlage, which was regulated by enzymes that degrade retinoic acid (RA). Transient manipulation of RA signaling, or reduction of Fgf8 expression, disrupted several features of HAA patterning, including photoreceptor distribution, ganglion cell density, and organization of interneurons. Notably, patterned expression of RA signaling components was also found in humans, suggesting that RA also plays a role in setting up the human fovea.