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Adv."],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:p>\n                    Pathogenic variants in\n                    <jats:italic toggle=\"yes\">ASXL3<\/jats:italic>\n                    underlie autism spectrum disorder (ASD), but how they perturb neural circuits and whether defects are reversible remain unclear. Here we show that\n                    <jats:italic toggle=\"yes\">Asxl3<\/jats:italic>\n                    haploinsufficiency in mice reduces cortical thickness and upper-layer projection neurons while increasing parvalbumin (PV) interneuron number and producing ASD-like behavioral abnormalities. Mechanistically,\n                    <jats:italic toggle=\"yes\">Asxl3<\/jats:italic>\n                    loss derepresses the thyroid hormone (TH)\u2013inactivating enzyme DIO3 via altered histone H2A monoubiquitination, depleting brain TH. Conditional deletion of the TH receptor\n                    <jats:italic toggle=\"yes\">Thra<\/jats:italic>\n                    in inhibitory neuron progenitors phenocopies the PV interneuron expansion, linking impaired TH signaling to PV circuit remodeling. Neonatal, but not adolescent, TH supplementation restores PV interneuron numbers and rescues behavior in\n                    <jats:italic toggle=\"yes\">\n                      Asxl3\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice, defining a critical early window for intervention. An intein-based AAV system that reconstitutes full-length ASXL3 normalizes cortical architecture and behavior in\n                    <jats:italic toggle=\"yes\">\n                      Asxl3\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice and drives efficient ASXL3 expression in non-human primate brain, establishing an ASXL3\u2013TH\u2013PV interneuron axis as a targetable pathway in ASD.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeh2640","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:59:49Z","timestamp":1790186389000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["An ASXL3\u2013thyroid hormone axis in parvalbumin interneurons controls autism-like behaviors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6054-1237","authenticated-orcid":true,"given":"Chaodong","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Neurology, Songjiang Research Institute, State Key Laboratory of Eye Health, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Songjiang Research Institute, State Key Laboratory of Eye Health, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Songjiang Research Institute, State Key Laboratory of Eye Health, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Songjiang Research Institute, State Key Laboratory of Eye Health, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-1633","authenticated-orcid":true,"given":"Shihao","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan University, Kunming, Yunnan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-923X","authenticated-orcid":true,"given":"Ailian","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, Songjiang Research Institute, State Key Laboratory of Eye Health, Songjiang Hospital Affiliated to 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