Retinoic acid signaling regulates spatiotemporal specification of human green and red cones.
Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002464&type=printable |
| _version_ | 1827331108623089664 |
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| author | Sarah E Hadyniak Joanna F D Hagen Kiara C Eldred Boris Brenerman Katarzyna A Hussey Rajiv C McCoy Michael E G Sauria James A Kuchenbecker Thomas Reh Ian Glass Maureen Neitz Jay Neitz James Taylor Robert J Johnston |
| author_facet | Sarah E Hadyniak Joanna F D Hagen Kiara C Eldred Boris Brenerman Katarzyna A Hussey Rajiv C McCoy Michael E G Sauria James A Kuchenbecker Thomas Reh Ian Glass Maureen Neitz Jay Neitz James Taylor Robert J Johnston |
| author_sort | Sarah E Hadyniak |
| collection | DOAJ |
| description | Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar M- and L-opsin mRNAs. M-opsin was observed before L-opsin expression during early human eye development, suggesting that M cones are generated before L cones. In adult human tissue, the early-developing central retina contained a mix of M and L cones compared to the late-developing peripheral region, which contained a high proportion of L cones. Retinoic acid (RA)-synthesizing enzymes are highly expressed early in retinal development. High RA signaling early was sufficient to promote M cone fate and suppress L cone fate in retinal organoids. Across a human population sample, natural variation in the ratios of M and L cone subtypes was associated with a noncoding polymorphism in the NR2F2 gene, a mediator of RA signaling. Our data suggest that RA promotes M cone fate early in development to generate the pattern of M and L cones across the human retina. |
| first_indexed | 2024-03-07T16:29:14Z |
| format | Article |
| id | doaj.art-1f0475e47bdc4d9385fdd1053392dcb8 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-07T16:29:14Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-1f0475e47bdc4d9385fdd1053392dcb82024-03-03T11:38:13ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-01-01221e300246410.1371/journal.pbio.3002464Retinoic acid signaling regulates spatiotemporal specification of human green and red cones.Sarah E HadyniakJoanna F D HagenKiara C EldredBoris BrenermanKatarzyna A HusseyRajiv C McCoyMichael E G SauriaJames A KuchenbeckerThomas RehIan GlassMaureen NeitzJay NeitzJames TaylorRobert J JohnstonTrichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar M- and L-opsin mRNAs. M-opsin was observed before L-opsin expression during early human eye development, suggesting that M cones are generated before L cones. In adult human tissue, the early-developing central retina contained a mix of M and L cones compared to the late-developing peripheral region, which contained a high proportion of L cones. Retinoic acid (RA)-synthesizing enzymes are highly expressed early in retinal development. High RA signaling early was sufficient to promote M cone fate and suppress L cone fate in retinal organoids. Across a human population sample, natural variation in the ratios of M and L cone subtypes was associated with a noncoding polymorphism in the NR2F2 gene, a mediator of RA signaling. Our data suggest that RA promotes M cone fate early in development to generate the pattern of M and L cones across the human retina.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002464&type=printable |
| spellingShingle | Sarah E Hadyniak Joanna F D Hagen Kiara C Eldred Boris Brenerman Katarzyna A Hussey Rajiv C McCoy Michael E G Sauria James A Kuchenbecker Thomas Reh Ian Glass Maureen Neitz Jay Neitz James Taylor Robert J Johnston Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. PLoS Biology |
| title | Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. |
| title_full | Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. |
| title_fullStr | Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. |
| title_full_unstemmed | Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. |
| title_short | Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. |
| title_sort | retinoic acid signaling regulates spatiotemporal specification of human green and red cones |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002464&type=printable |
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