Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

Summary The brain is assembled during development by both innate and experience-dependent mechanisms 1–7 , but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components 7–9 . Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs 10 and central neurons 11–16 . Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog 17 and gene expression atlas 18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz ( atoh7 - ) mutants, in which RGCs do not form 19 . Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area 20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.