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 co-regulation 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.