{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:35:28Z","timestamp":1788622528289,"version":"build-2803163510"},"reference-count":80,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007379","name":"Fondation pour l'Aide \u00e0 la Recherche sur la Scl\u00e9rose en Plaques","doi-asserted-by":"publisher","award":["Role of RXRg in T3\u2010mediated oligodendrocyte differentiation"],"award-info":[{"award-number":["Role of RXRg in T3\u2010mediated oligodendrocyte differentiation"]}],"id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Overcoming remyelination failure is one of the main targets in therapeutic strategies for multiple sclerosis. This process requires the differentiation of oligodendrocyte precursor cells (OPCs) to mature myelinating oligodendrocytes (OLs), a process known to be controlled by thyroid hormone, nuclear receptors, and sonic hedgehog (SHH). Retinoid X receptor gamma (RXRg) is one of the nuclear receptors acting as a positive regulator of remyelination, but little is known about its mechanisms of function. Using transcriptomic and pharmacological analysis of primary neural stem cell\u2010derived OPCs, we show that RXRg is involved in the induction of the thyroid hormone\u2010driven differentiation process and in refining it toward an oligodendrogenic cell fate. RXRg also emerged as an important negative modulator of SHH expression and signaling, as\n                    <jats:italic>Shh<\/jats:italic>\n                    and additional genes from this pathway were found to be strongly upregulated in\n                    <jats:italic>Rxrg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    OPCs. An inhibition of SHH signaling by cyclopamine or GANT61 entirely normalized the differentiation deficit of\n                    <jats:italic>Rxrg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    OPCs, but also myelination of newly generated\n                    <jats:italic>Rxrg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    OLs. Such data indicate a key role of SHH hyperactivity in the oligodendrogenesis block associated with the absence of RXRg. Importantly, hyperactivation of the SHH pathway by purmorphamine or SAG inhibited the oligodendrogenesis and myelination potential of wild\u2010type OPCs, indicating that SHH hyperactivity can also be a sufficient factor to block OPC differentiation. These results point to RXRg as an important regulator of SHH pathway signaling and underline the need of an optimal, fine\u2010tuning of SHH signaling to assure successful oligodendrogenesis.\n                  <\/jats:p>","DOI":"10.1002\/glia.70151","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:15:00Z","timestamp":1775283300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>RXR<\/scp>\n                    Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-4261","authenticated-orcid":false,"given":"Vito Antonio","family":"Baldassarro","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U 1258, Illkirch, Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"Department of Veterinary Medical Science University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Brassart","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U 1258, Illkirch, Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Fraulob","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U 1258, Illkirch, Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-8477","authenticated-orcid":false,"given":"Laura","family":"Calz\u00e0","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-3185","authenticated-orcid":false,"given":"Wojciech","family":"Krezel","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U 1258, Illkirch, Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/BIO.20135041"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTU638"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SCR.2017.05.011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3791\/61988"},{"key":"e_1_2_10_6_1","first-page":"389","volume-title":"Vitamins and Hormones","author":"Baldassarro V. 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