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

Abstract

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.

New twists in the evolution of retinal direction selectivity

“…Correspondingly, this also means that probably all these other tetrapods have starburst cells, and if not, it would mean that these cells were lost rather than that they never existed. The presence of starburst cells in the eyes of most if not all vertebrates was long suspected—after all, vertebrate retinas consistently have ChAT [ 8 , 9 ]. However, it had remained unclear if these cholinergic bands correspond to starburst cells.…”

“…Only a few months ago learned that within mammals, and perhaps beyond, most retinal neurons can be molecularly linked across all extant species [ 13 ]. Already the jawless lampreys, representatives of the evolutionarily most distant extant vertebrates, feature transcriptomic signatures of a great many usual-suspect neurons—notably including not 2 but 4 transcriptomic signatures of cholinergic amacrine cells [ 9 ]! Another recent preprint [ 14 ] reported the zebrafish ortholog of the mammalian rod bipolar cell, plus their associated circuits, which together underpin our own sense of night vision.…”