Retina-derived signals control pace of neurogenesis in visual brain areas but not circuit configuration
Brain development is orchestrated by both innate and experience-dependent mechanisms, but their relative contributions are often difficult to resolve. Here we asked if and how central visual areas are altered in a vertebrate brain depleted of any and all signals from retinal ganglion cells throughout development. We transcriptionally profiled neurons in pretectum, thalamus and other retinorecipient areas of larval zebrafish and searched for changes in lakritz mutants that lack all retinal connections. Although individual genes are dysregulated, the complete set of 77 neuronal types develops in apparently normal proportions, at normal locations, and along normal differentiation trajectories. Strikingly, the cell-cycle exits of proliferating progenitors in these areas are delayed, and a greater fraction of early postmitotic precursors remain uncommitted or are diverted to a glial fate. Optogenetic stimulation targeting groups of neurons normally involved in processing visual information evokes behaviors indistinguishable from wildtype. In conclusion, we show that signals emitted by retinal axons influence the pace of neurogenesis in visual areas, but do not detectably affect the specification or wiring of downstream neurons. Overall design: Tg(HGn12C:GFP) or [Tg(Gal4s1026t) X Tg(UAS:GFP)] larvae were sorted for GFP expression 24 hours after fertilization. All single-cell experiments were performed at 6 days after fertilization. To obtain unrelated WT, pigmented larvae were used from Tg(HGn12C:GFP) pigmented males or females crossed with WT TLN, which are homozygous mutant for mitfa. To obtain lakritz mutant and sibling WT larvae, Tg(HGn12C:GFP) lakritz heterozygote adults were crossed with adult lakritz heterozygotes. For experiments with lakritz larvae, only lakritz mutants were collected; for other experiments, they were discarded. For single-cell experiments larvae were rapidly decapitated and processed for cell dissociation followed by FACS of labelled cells.