Co-Conservation of synaptic gene expression and circuitry in collicular neurons

The superior colliculus (SC), a midbrain sensorimotor hub, is anatomically and functionally similar across vertebrates, but how its cell types have evolved is unclear. Using single-nucleus transcriptomics, we compared the SC’s molecular and cellular organization in mice, tree shrews, and humans. Despite over 96 million years of evolutionary divergence, we identified ~30 consensus neuronal subtypes, including Cbln2+ neurons that form the SC-pulvinar circuit in mice and tree shrews. Synapse-related genes were among the most conserved in the SC, unlike neocortex, suggesting co-conservation of synaptic genes and collicular circuitry. In contrast, cilia-related genes diverged significantly across species, highlighting the potential importance of the neuronal primary cilium in SC evolution. Additionally, we identified an inhibitory SC neuron in tree shrews and humans but not mice. Our findings reveal that the SC has evolved by conserving neuron subtypes, synaptic genes, and circuitry, while diversifying ciliary gene expression and an inhibitory neuron subtype. The molecular and cellular evolution of the superior colliculus, a key visual center, is unclear. Liu et al. revealed conserved and species-specific cell types, genes, and circuits across mice, tree shrews, and humans by single-cell transcriptomics.