Molecular Characterization of the Sea Lamprey Retina Illuminates the Evolutionary Origin of Retinal Cell Types

The lamprey, a primitive jawless vertebrate whose ancestors diverged from all other vertebrates over 500 million years ago, offers a unique window into the primordial formation of the retina. Using single-cell RNA-sequencing, we characterized retinal cell types in lamprey and compared their molecular differentiation and regulatory networks with those in mouse and other jawed vertebrates. Our analysis revealed six cell classes and 74 distinct cell types. We discovered multiple conserved cell types shared between jawless and jawed lineages, including notably rods and cones, ON and OFF bipolar cells, and starburst amacrine cells. The conservation of these cell types indicates their emergence early in vertebrate evolution, highlighting the primal designs of retinal circuits for the rod pathway, ON-OFF discrimination, and direction selectivity. In contrast to this evidence for conservation, the pathways of diversification for amacrine cells and retinal ganglion cells appear to have distinctly diverged between the two lineages. Furthermore, we inferred master regulators in specifying retinal cell classes in both lamprey and macaque and identified common regulatory elements across species, underscoring the ancestral nature of the molecular origins governing retinal cell classes. Altogether, our characterization of the lamprey retina illuminates the evolutionary origin of visual processing in the retina. ### Competing Interest Statement The authors have declared no competing interest.