{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:04:08Z","timestamp":1791947048841,"version":"4.3.4"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vertebrate color vision results from the specification of photoreceptor subtypes expressing distinct opsins. Thyroid hormone (TH) and its receptor TR\u03b22 are essential regulators of long-wavelength-sensitive (LWS) cone development, but their ligand-dependent roles in regulating cone subtype fate remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated how varying TH availability and TR\u03b22 overexpression impact cone photoreceptor diversity and opsin expression using a gain-of-function transgenic zebrafish line (<jats:italic>crx:tr\u03b22<\/jats:italic>), which expresses TR\u03b22 in all photoreceptors, and manipulated TH levels through T3 supplementation or ablation of the thyroid gland. Samples were analyzed through a combination of hybridization chain reaction <jats:italic>in situ<\/jats:italic> hybridization, confocal microscopy, and quantitative RT-PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>we found evidence consistent with the hypothesis that unliganded TR\u03b22 predominantly promotes <jats:italic>lws2<\/jats:italic> expression, while liganded TR\u03b22 upregulates <jats:italic>lws1<\/jats:italic>, following a dose-dependent and temporally dynamic pattern. Overexpression of TR\u03b22 promoted co-expression of <jats:italic>lws2<\/jats:italic> in non-LWS cones, suggesting possible photoreceptor transfating. TH supplementation amplified these effects and induced changes in numbers and morphologies of cone subtypes with no obvious evidence of cell death. We also identified spatially distinct expression of key TH regulatory genes (<jats:italic>dio2<\/jats:italic>, <jats:italic>dio3b<\/jats:italic>, <jats:italic>mct8<\/jats:italic>) in the retina and retinal pigment epithelium, which responded dynamically to manipulation of TH levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that TR\u03b22 exerts differential effects on cone opsin expression depending on presence and quantity of ligand.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1697930","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:05:53Z","timestamp":1760969153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Thyroid hormone receptor beta-2 (TR\u03b22) overexpression modulates photoreceptor phenotype diversity in a ligand-dependent manner"],"prefix":"10.3389","volume":"13","author":[{"given":"Emmanuel","family":"Owusu Poku","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Fonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney P.","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Mackin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Stenkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1073\/pnas.0809439106","article-title":"Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development","volume":"106","author":"Alvarez-Delfin","year":"2009","journal-title":"Proc. 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