Independent Genomic Control of Neuronal Number across Retinal Cell Types

The sizes of different neuronal populations within the CNS are precisely controlled, but whether neuronal number is coordinated between cell types is unknown. We examined the covariance structure of 12 different retinal cell types across 30 genetically distinct lines of mice, finding minimal covariation when comparing synaptically connected or developmentally related cell types. Variation mapped to one or more genomic loci for each cell type, but rarely were these shared, indicating minimal genetic coregulation of final number. Multiple genes, therefore, participate in the specification of the size of every population of retinal neuron, yet genetic variants work largely independent of one another during development to modulate those numbers, yielding substantial variability in the convergence ratios between pre- and postsynaptic populations. Density-dependent cellular interactions in the outer plexiform layer overcome this variability to ensure the formation of neuronal circuits that maintain constant retinal coverage and complete afferent sampling. [Display omitted] •Mouse strains exhibit large variations in retinal cell number•Minimal covariation in cell number exists between different retinal cell types•Variation between the cell types maps to independent genomic loci•Variation in pre- and postsynaptic cell number modulates dendritic differentiation Keeley et al. find that the numbers of different types of retinal neurons vary independently of one another. Strong determinants of variation map to independent loci. Thus, retinal neuron cell-type allocation is not tightly correlated or coregulated. Rather, density-dependent cellular interactions overcome variability to maintain coverage and complete afferent sampling.