Dscamb regulates cone mosaic formation in zebrafish via filopodium-mediated homotypic recognition.

Cone photoreceptors assemble to form a regular mosaic pattern in vertebrate retinas. In zebrafish, four distinct spectral cone types (red, green, blue, and ultraviolet), form a lattice-like pattern. However, the mechanism of cone mosaic formation has been unknown. Here we show that Down Syndrome Cell Adhesion Molecule b (Dscamb) regulates the cone mosaic pattern in zebrafish, especially via red-cone spacing. During photoreceptor differentiation, newly formed cones extend filopodium-like processes laterally to apical surfaces of neighboring cones. Interestingly, red cones extend filopodia, but promptly retract them when they meet their own cone type, suggesting filopodium-mediated, homotypic recognition and self-avoidance. This self-avoidance is compromised in zebrafish dscamb mutants, leading to abnormal clustering of red cones and subsequent disruption of regular cone spacing. Thus, apical filopodium-mediated spacing of the same cone type depends on Dscamb and is essential for cone mosaic formation in zebrafish.