Hu Dongpeng, Masai Ichiro
Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan.
Nat Commun. 2025 Mar 25;16(1):2501. doi: 10.1038/s41467-025-57506-1.
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.
视锥光感受器在脊椎动物视网膜中组装形成规则的镶嵌模式。在斑马鱼中，四种不同光谱类型的视锥细胞（红色、绿色、蓝色和紫外线）形成类似晶格的模式。然而，视锥镶嵌模式的形成机制一直未知。在此我们表明，唐氏综合征细胞粘附分子b（Dscamb）调节斑马鱼中的视锥镶嵌模式，特别是通过红锥间距。在光感受器分化过程中，新形成的视锥细胞向相邻视锥细胞的顶端表面横向延伸丝状伪足样突起。有趣的是，红锥细胞会延伸丝状伪足，但当它们遇到自身视锥细胞类型时会迅速缩回，这表明丝状伪足介导了同型识别和自我回避。在斑马鱼dscamb突变体中，这种自我回避受到损害，导致红锥细胞异常聚集，并随后破坏规则的视锥间距。因此，同一视锥细胞类型的顶端丝状伪足介导的间距依赖于Dscamb，并且对于斑马鱼中视锥镶嵌模式的形成至关重要。
