The extreme diversity of retinal amacrine cells has deep evolutionary roots
- 14 August 2026
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 12 (33)
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.Keywords
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)
This publication has 93 references indexed in Scilit:
- Multiple cell types form the VIP amacrine cell populationJournal of Comparative Neurology, 2017
- Lhx9 Is Required for the Development of Retinal Nitric Oxide-Synthesizing Amacrine Cell SubtypeMolecular Neurobiology, 2017
- Characterization of small‐field bistratified amacrine cells in macaque retina labeled by antibodies against synaptotagmin‐2Journal of Comparative Neurology, 2012
- Birthdays of retinal amacrine cell subtypes are systematically related to their molecular identity and soma positionJournal of Comparative Neurology, 2009
- Synaptic connections of the narrow‐field, bistratified rod amacrine cell (AII) in the rabbit retinaJournal of Comparative Neurology, 1992
- Morphology and mosaics of VIP‐like immunoreactive neurons in the retina of the rhesus monkeyJournal of Comparative Neurology, 1991
- Reconstructing ancestral character states under Wagner parsimonyMathematical Biosciences, 1987
- ‘Starburst’ amacrine cells and cholinergic neurons: mirror-symmetric ON and OFF amacrine cells of rabbit retinaBrain Research, 1983
- Localization of neuroactive substances in the vertebrate retina: Evidence for lamination in the inner plexiform layerVision Research, 1983
- A bistratified amacrine cell and synaptic circuitry in the inner plexiform layer of the retinaBrain Research, 1975