biostudies-literatureUnknown16(1)Hu DOkinawa Institute of Science and Technology Graduate UniversityCone 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, leadNature communications2501https://www.ebi.ac.uk/biostudies/studies/S-EPMC11937385biostudies-literatureDscamb regulates cone mosaic formation in zebrafish via filopodium-mediated homotypic recognition.PMC11937385Hu DMasai IfalseDscamb 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, lead2025-01-01T00:00:00Z2025 Mar2026-07-15T14:39:33.056Z2026-07-07T03:08:26.964ZS-EPMC119373854013328110.1038/s41467-025-57506-1