{"doi":"10.1371/journal.pbio.3002464","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.","journal":"PLoS Biology","year":2024,"id":423562,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":816324,"name":"Joanna F. D. Hagen","orcid":"0000-0002-7576-6137","position":1,"is_corresponding":false},{"id":374756,"name":"Kiara C. Eldred","orcid":"0000-0002-4067-8639","position":2,"is_corresponding":false},{"id":816323,"name":"Boris Brenerman","orcid":"0000-0001-9252-8184","position":3,"is_corresponding":false},{"id":481482,"name":"Katarzyna A. Hussey","orcid":"0000-0002-5046-2815","position":4,"is_corresponding":false},{"id":49046,"name":"Rajiv C. McCoy","orcid":"0000-0003-0615-146X","position":5,"is_corresponding":false},{"id":53923,"name":"Michael E.G. Sauria","orcid":"0000-0001-5556-9446","position":6,"is_corresponding":false},{"id":332650,"name":"James A. Kuchenbecker","orcid":"0000-0002-8603-7693","position":7,"is_corresponding":false},{"id":90383,"name":"Thomas A. Reh","orcid":"0000-0002-3524-0886","position":8,"is_corresponding":false},{"id":104361,"name":"Ian A. Glass","orcid":"0000-0001-6762-8407","position":9,"is_corresponding":false},{"id":342656,"name":"Maureen Neitz","orcid":"0000-0002-5404-3343","position":10,"is_corresponding":false},{"id":339552,"name":"Jay Neitz","orcid":"0000-0003-3877-6712","position":11,"is_corresponding":false},{"id":19436,"name":"James Taylor","orcid":"0000-0001-5079-840X","position":12,"is_corresponding":false},{"id":259949,"name":"Robert J. Johnston","orcid":"0000-0002-5775-6218","position":13,"is_corresponding":false},{"id":816322,"name":"Sarah E. Hadyniak","orcid":"0000-0003-2768-0037","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:58:01.889748Z","pmid":"38206904","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}