Abstract
Amacrine cells (ACs) comprise a heterogeneous class of inhibitory neurons in the vertebrate retina, exhibiting morphological and functional complexity rivaling that of cortical interneurons. Here, we integrate single-cell and single-nucleus transcriptomic atlases from 24 vertebrate species to reconstruct the evolutionary origins of this extreme diversity. We identify 42 orthologous AC types, most of which exhibit a one-to-one correspondence across amniotes and, in many cases, across vertebrates. While core molecular identities are conserved, AC types vary in abundance and gene expression across species, likely reflecting adaptations to distinct visual ecologies. AC diversity scales with that of retinal ganglion cells (RGCs), indicative of coevolution. Last, we suggest that ACs arose from an AC-RGC hybrid precursor, with glycinergic ACs diverging early in vertebrate evolution, followed by a bifurcation between RGCs and GABAergic ACs. Together, these findings establish a unified evolutionary framework for understanding the diversity, development, and function of a class of inhibitory neurons across vertebrates.
Funding Information
  • National Institutes of Health (EY028625)
  • National Institutes of Health (EY024265)
  • National Institutes of Health (F31EY038101)
  • National Institutes of Health (EY028633)
  • National Institutes of Health (MH105960)
  • National Institutes of Health (U01NS136405)
  • Research Corporation for Science Advancement (SA-MND-2023-031)
  • Glaucoma Research Foundation
  • McKnight Foundation
  • National Science Foundation CRCNS (2309039)
  • BrightFocus Foundation (National Glaucoma Award)
  • Howard Hughes Medical Institute Hanna H. Gray
  • Burroughs Wellcome Fund Postdoctoral Diversity Enrichment Program (1287193)
  • National Science Foundation CRCNS (2309039)
  • European Research Council DEEPRETINA (101045253)

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