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Both\n                    <jats:italic toggle=\"yes\">CYP26A1<\/jats:italic>\n                    mutant organoids and high RA conditions increased the number of S cones and reduced the number of M\/L cones in retinal organoids. In contrast, sustained TH signaling promoted the generation of M\/L-opsin-expressing cones and induced M\/L-opsin expression in S-opsin-expressing cones, showing that cone fate is plastic. Our data suggest that CYP26A1 degrades RA to specify M\/L cones and limit S cones and that continuous DIO2 expression sustains high levels of TH to transition S-opsin-expressing cones into M\/L cone fate, resulting in the foveola containing only M\/L cones. Given the vulnerability of the foveola in macular degeneration and other retinal disorders, these findings provide a mechanistic framework for engineering organoids for therapeutic applications.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2510799123","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:32:06Z","timestamp":1771000326000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["A cell fate specification and transition mechanism for human foveolar cone subtype patterning"],"prefix":"10.1073","volume":"123","author":[{"given":"Katarzyna A.","family":"Hussey","sequence":"first","affiliation":[{"name":"Department of Biology, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-8639","authenticated-orcid":false,"given":"Kiara C.","family":"Eldred","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University","place":["Baltimore"]},{"name":"Department of Neurobiology and Biophysics, University of Washington","place":["Seattle, Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-668X","authenticated-orcid":false,"given":"Clayton P.","family":"Santiago","sequence":"additional","affiliation":[{"name":"The Solomon H. 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