{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:09:47Z","timestamp":1792145387903,"version":"4.4.0"},"reference-count":23,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":2120,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II\u2013IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining the disproportionate layering. Premature differentiation was associated with an increased generation of outer radial glia (oRG) and TBR2-expressing basal progenitors, as well as increased generation of early-born post-mitotic projection neurons. Atrx deletion also reduced the fidelity of mitotic spindle orientation in apical progenitors, where mutant cells were often oriented at non-parallel angles of division relative to the ventricular surface. We conclude that ATRX is required for correct lamination of the mouse neocortex by regulating the timing of neuroprogenitor cell differentiation.<\/jats:p>","DOI":"10.1242\/bio.20148730","type":"journal-article","created":{"date-parts":[[2014,11,14]],"date-time":"2014-11-14T06:28:10Z","timestamp":1415946490000},"page":"1158-1163","source":"Crossref","is-referenced-by-count":39,"title":["ATRX is required for maintenance of the neuroprogenitor cell pool in the embryonic mouse brain"],"prefix":"10.1242","volume":"3","author":[{"given":"Kieran","family":"Ritchie","sequence":"first","affiliation":[{"name":"Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Ashley","family":"Watson","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Davidson","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie G.","family":"B\u00e9rub\u00e9","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"2021111216365616400_b1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.bandc.2010.08.011","article-title":"Asymmetric prefrontal cortex functions predict asymmetries in number space.","volume":"74","author":"Bachmann","year":"2010","journal-title":"Brain Cogn."},{"key":"2021111216365616400_b2","doi-asserted-by":"publisher","first-page":"e1001137","DOI":"10.1371\/journal.pgen.1001137","article-title":"Loss of maternal ATRX results in centromere instability and aneuploidy in the mammalian oocyte and pre-implantation embryo.","volume":"6","author":"Baumann","year":"2010","journal-title":"PLoS Genet."},{"key":"2021111216365616400_b3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1093\/hmg\/9.4.539","article-title":"Cell cycle-dependent phosphorylation of the ATRX protein correlates with changes in nuclear matrix and chromatin association.","volume":"9","author":"B\u00e9rub\u00e9","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2021111216365616400_b4","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1172\/JCI200522329","article-title":"The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis.","volume":"115","author":"B\u00e9rub\u00e9","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2021111216365616400_b5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0896-6273(95)90065-9","article-title":"T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex.","volume":"15","author":"Bulfone","year":"1995","journal-title":"Neuron"},{"key":"2021111216365616400_b6","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.neuron.2005.04.014","article-title":"Cortical neuron specification: it has its time and place.","volume":"46","author":"Campbell","year":"2005","journal-title":"Neuron"},{"key":"2021111216365616400_b7","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/j.1600-0609.2006.00628.x","article-title":"A novel mutation in the last exon of ATRX in a patient with alpha-thalassemia myelodysplastic syndrome.","volume":"76","author":"Costa","year":"2006","journal-title":"Eur. J. Haematol."},{"key":"2021111216365616400_b8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2003.12.012","article-title":"ATRX, a member of the SNF2 family of helicase\/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytes.","volume":"272","author":"De La Fuente","year":"2004","journal-title":"Dev. Biol."},{"key":"2021111216365616400_b9","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1101\/gad.566910","article-title":"The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3.","volume":"24","author":"Dran\u00e9","year":"2010","journal-title":"Genes Dev."},{"key":"2021111216365616400_b10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/0092-8674(95)90287-2","article-title":"Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).","volume":"80","author":"Gibbons","year":"1995","journal-title":"Cell"},{"key":"2021111216365616400_b11","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.cell.2010.01.003","article-title":"Distinct factors control histone variant H3.3 localization at specific genomic regions.","volume":"140","author":"Goldberg","year":"2010","journal-title":"Cell"},{"key":"2021111216365616400_b12","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/ncb1673","article-title":"Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis.","volume":"10","author":"Konno","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"2021111216365616400_b13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.conb.2008.05.006","article-title":"The determination of projection neuron identity in the developing cerebral cortex.","volume":"18","author":"Leone","year":"2008","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021111216365616400_b14","doi-asserted-by":"publisher","first-page":"14075","DOI":"10.1073\/pnas.1008850107","article-title":"Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres.","volume":"107","author":"Lewis","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021111216365616400_b15","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1093\/hmg\/ddr163","article-title":"Functional significance of mutations in the Snf2 domain of ATRX.","volume":"20","author":"Mitson","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2021111216365616400_b16","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.neuron.2011.09.022","article-title":"Mouse inscuteable induces apical-basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex.","volume":"72","author":"Postiglione","year":"2011","journal-title":"Neuron"},{"key":"2021111216365616400_b17","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1126\/science.183.4123.425","article-title":"Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition.","volume":"183","author":"Rakic","year":"1974","journal-title":"Science"},{"key":"2021111216365616400_b18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1083\/jcb.200706083","article-title":"Loss of ATRX leads to chromosome cohesion and congression defects.","volume":"180","author":"Ritchie","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021111216365616400_b19","doi-asserted-by":"publisher","first-page":"12570","DOI":"10.1523\/JNEUROSCI.4048-08.2008","article-title":"Neuronal death resulting from targeted disruption of the Snf2 protein ATRX is mediated by p53.","volume":"28","author":"Seah","year":"2008","journal-title":"J. Neurosci."},{"key":"2021111216365616400_b20","doi-asserted-by":"publisher","first-page":"3683","DOI":"10.1523\/JNEUROSCI.4773-10.2011","article-title":"Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors.","volume":"31","author":"Shitamukai","year":"2011","journal-title":"J. Neurosci."},{"key":"2021111216365616400_b21","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/nn.2807","article-title":"A new subtype of progenitor cell in the mouse embryonic neocortex.","volume":"14","author":"Wang","year":"2011","journal-title":"Nat. Neurosci."},{"key":"2021111216365616400_b22","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1172\/JCI65634","article-title":"Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span.","volume":"123","author":"Watson","year":"2013","journal-title":"J. Clin. Invest."},{"key":"2021111216365616400_b23","doi-asserted-by":"publisher","first-page":"10635","DOI":"10.1073\/pnas.1937626100","article-title":"The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.","volume":"100","author":"Xue","year":"2003","journal-title":"Proc. Natl. Acad. Sci. 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