{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:19Z","timestamp":1786978519281,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,4,24]],"date-time":"2013-04-24T00:00:00Z","timestamp":1366761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NIH","award":["NS031348"],"award-info":[{"award-number":["NS031348"]}]},{"name":"TJL Cancer Center Support","award":["CA034196"],"award-info":[{"award-number":["CA034196"]}]},{"name":"Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Id2 \u00a0is a helix-loop-helix transcription factor essential for normal development, and its expression is dysregulated in many human neurological conditions. Although it is speculated that elevated \u00a0Id2 \u00a0levels contribute to the pathogenesis of these disorders, it is unknown whether dysregulated \u00a0Id2 \u00a0expression is sufficient to perturb normal brain development or function. Here, we show that mice with elevated \u00a0Id2 \u00a0expression during embryonic stages develop microcephaly, and that females in particular are prone to generalized tonic-clonic seizures. Analyses of \u00a0Id2 \u00a0transgenic brains indicate that \u00a0Id2 \u00a0activity is highly cell context specific: elevated \u00a0Id2 \u00a0expression in naive neural stem cells (NSCs) in early neuroepithelium induces apoptosis and loss of NSCs and intermediate progenitors. Activation of \u00a0Id2 \u00a0in maturing neuroepithelium results in less severe phenotypes and is accompanied by elevation of G1 cyclin expression and p53 target gene expression. In contrast, activation of \u00a0Id2 \u00a0in committed intermediate progenitors has no significant phenotype. Functional analysis with \u00a0Id2-overexpressing and \u00a0Id2-null NSCs shows that \u00a0Id2 \u00a0negatively regulates NSC self-renewal in vivo, in contrast to previous cell culture experiments. Deletion of \u00a0p53 \u00a0function from \u00a0Id2-transgenic brains rescues apoptosis and results in increased incidence of brain tumors. Furthermore, \u00a0Id2 \u00a0overexpression normalizes the increased self-renewal of \u00a0p53-null NSCs, suggesting that \u00a0Id2 \u00a0activates and modulates the p53 pathway in NSCs. Together, these data suggest that elevated \u00a0Id2 \u00a0expression in embryonic brains can cause deregulated NSC self-renewal, differentiation, and survival that manifest in multiple neurological outcomes in mature brains, including microcephaly, seizures, and brain tumors.<\/jats:p>","DOI":"10.1002\/stem.1351","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T23:44:40Z","timestamp":1360194280000},"page":"1010-1021","source":"Crossref","is-referenced-by-count":24,"title":["Elevated\n                    <i>Id2<\/i>\n                    Expression Results in Precocious Neural Stem Cell Depletion and Abnormal Brain Development"],"prefix":"10.1093","volume":"31","author":[{"given":"Hee Jung","family":"Park","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingi","family":"Hong","sequence":"additional","affiliation":[{"name":"The Jackson 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