@article{4231, keywords = {Adults, Bright field microscopy, In Situ Hybridization, organoids, Photoreceptors, RNA hybridization, Retina, Transfection}, author = {Sarah E. Hadyniak and Joanna F. D. Hagen and Kiara C. Eldred and Boris Brenerman and Katarzyna A. Hussey and Rajiv C. McCoy and Michael E. G. Sauria and James A. Kuchenbecker and Thomas Reh and Ian Glass and Maureen Neitz and Jay Neitz and James Taylor and Robert J. Johnston Jr}, title = {Retinoic acid signaling regulates spatiotemporal specification of human green and red cones}, abstract = {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.}, year = {0}, journal = {PLOS Biology}, volume = {22}, pages = {e3002464}, month = {Jan 11, 2024}, issn = {1545-7885}, url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002464}, doi = {10.1371/journal.pbio.3002464}, language = {en}, }