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To determine the role of UTX (also known as KDM6A), a demethylase of histone H3K27, in neural development, we generated\n                    <jats:italic>Utx<\/jats:italic>\n                    \u2010deficient mice in neural stem\/progenitor cells (NSPCs). Since\n                    <jats:italic>Utx<\/jats:italic>\n                    is an X chromosome\u2010specific gene, the genotypes are sex\u2010dependent; female mice lose both\n                    <jats:italic>Utx<\/jats:italic>\n                    alleles (\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    ), and male mice lose one\n                    <jats:italic>Utx<\/jats:italic>\n                    allele yet retain one\n                    <jats:italic>Uty<\/jats:italic>\n                    allele, the counterpart of\n                    <jats:italic>Utx<\/jats:italic>\n                    on the Y chromosome (\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\n                      \u0394\/\n                      <jats:italic>Uty<\/jats:italic>\n                    <\/jats:sup>\n                    ). We found that\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    mice exhibited fetal ventriculomegaly and died soon after birth. Immunofluorescence staining and EdU labeling revealed a significant increase in NSPCs and a significant decrease in intermediate\u2010progenitor and differentiated neural cells. Molecular analyses revealed the downregulation of pathways related to DNA replication and increased H3K27me3 levels around the transcription start sites in\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    NSPCs. These results indicate that UTX globally regulates the expression of genes required for proper neural development in NSPCs, and UTX deficiency leads to impaired cell cycle exit, reduced differentiation, and neonatal death. Interestingly, although\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\n                      \u0394\/\n                      <jats:italic>Uty<\/jats:italic>\n                    <\/jats:sup>\n                    mice survived the postnatal period, most died of hydrocephalus, a clinical feature of Kabuki syndrome, a congenital anomaly involving\n                    <jats:italic>UTX<\/jats:italic>\n                    mutations. Our findings provide novel insights into the role of histone modifiers in neural development and suggest that\n                    <jats:italic>Utx<\/jats:italic>\n                    <jats:sup>\n                      \u0394\/\n                      <jats:italic>Uty<\/jats:italic>\n                    <\/jats:sup>\n                    mice are a potential disease model for Kabuki syndrome.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201002rr","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T07:11:47Z","timestamp":1669101107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>UTX<\/scp>\n                    deficiency in neural stem\/progenitor cells results in impaired neural development, fetal ventriculomegaly, and postnatal death"],"prefix":"10.1096","volume":"36","author":[{"given":"Miho","family":"Koizumi","sequence":"first","affiliation":[{"name":"Field of 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