AbstractIn higher mammals, the primary visual cortex (V1) is organized into diverse tuning maps of visual features such as orientation, spatial frequency and ocular dominance. The topography of these maps is observed to intersect orthogonally, implying that a developmental principle for efficient tiling of sensory modules may exist. However, it remains unclear how such a systematic relationship among cortical tuning maps could develop. Here, we show that the orthogonal organization of tuning modules already exist in retinal ganglion cell (RGC) mosaics, and that this provides a blueprint of the orthogonal organization in V1. Firstly, from the analysis of multi-electrode recording data in V1, we found that the ON-OFF subregion distance of receptive fields varies periodically across the cortical surface, strongly correlated to ocular dominance and spatial frequency in the area. Further, the ON-OFF alignment angle, that is orthogonal to the ON-OFF distance, appears to correlate with orientation tuning. These suggest that the orthogonal organization in V1 may originate from the spatial organization of the ON-OFF receptive fields in the bottom-up projections, and this scenario was tested from analysis of the RGC mosaics data in monkeys and cats. We found that the ON-OFF RGC distance and ON-OFF angle of neighbouring RGCs are organized into a topographic tiling across mosaics, analogous to the orthogonal intersection of cortical tuning maps. These findings suggest that the regularly structured ON-OFF patterns mirrored from a retina may initiate efficient tiling of functional domains in V1.HighlightsOrthogonal organization of visual tuning maps are observed in both V1 and the retinaCortical tuning maps are correlated with the profile of ON-OFF feedforward projectionsThe profile of ON-OFF receptive fields varies periodically across the V1 surfaceRegularly structured RGC patterns initiate the orthogonal tiling of sensory modules in V1