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Indeed, T-box brain1 (Tbr1) is a TF crucial for the formation of neocortical layer VI, and mutations and microdeletions in that gene are associated with malformations in the human cerebral cortex, alterations that accompany autism spectrum disorder (ASD). Interestingly, Tbr1 upregulation has also been related to the occurrence of ASD-like symptoms, although limited studies have addressed the effect of increased Tbr1 levels during neocortical development. Here, we analysed the impact of Tbr1 misexpression in mouse neural progenitor cells (NPCs) at embryonic day 14.5 (E14.5), when they mainly generate neuronal layers II\u2013IV. By E18.5, cells accumulated in the intermediate zone and in the deep cortical layers, whereas they became less abundant in the upper cortical layers. In accordance with this, the proportion of Sox5\n                    <jats:sup>+<\/jats:sup>\n                    cells in layers V\u2013VI increased, while that of Cux1\n                    <jats:sup>+<\/jats:sup>\n                    cells in layers II\u2013IV decreased. On postnatal day 7, fewer defects in migration were evident, although a higher proportion of Sox5\n                    <jats:sup>+<\/jats:sup>\n                    cells were seen in the upper and deep layers. The abnormal neuronal migration could be partially due to the altered multipolar-bipolar neuron morphologies induced by Tbr1 misexpression, which also reduced dendrite growth and branching, and disrupted the\n                    <jats:italic>corpus callosum<\/jats:italic>\n                    . Our results indicate that Tbr1 misexpression in cortical NPCs delays or disrupts neuronal migration, neuronal specification, dendrite development and the formation of the callosal tract. Hence, genetic changes that provoke ectopic Tbr1 upregulation during development could provoke cortical brain malformations.\n                  <\/jats:p>","DOI":"10.1007\/s12035-022-02936-x","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:02:56Z","timestamp":1656932576000},"page":"5750-5765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Tbr1 Misexpression Alters Neuronal Development in the Cerebral Cortex"],"prefix":"10.1007","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3086-9762","authenticated-orcid":false,"given":"Inmaculada","family":"Crespo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Pignatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Kinare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor R.","family":"M\u00e9ndez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Esgleas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Rom\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Canals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubha","family":"Tole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-0250","authenticated-orcid":false,"given":"Carlos","family":"Vicario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"issue":"1","key":"2936_CR1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1523\/JNEUROSCI.2899-04.2005","volume":"25","author":"C Englund","year":"2005","unstructured":"Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, Kowalczyk T, Hevner RF (2005) Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. 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Science 364(6441):685\u2013689. https:\/\/doi.org\/10.1126\/science.aav8130","journal-title":"Science"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-02936-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-022-02936-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-02936-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T10:04:12Z","timestamp":1661162652000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-022-02936-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,4]]},"references-count":77,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["2936"],"URL":"https:\/\/doi.org\/10.1007\/s12035-022-02936-x","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,4]]},"assertion":[{"value":"1 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"All animal care and handling were carried out in accordance with the European Union guidelines (directive 2010\/63\/EU) and Spanish legislation (Law 32\/2007 and RD 53\/2013). The protocols were approved by the Ethics Committees of the Consejo Superior de Investigaciones Cient\u00edficas (CSIC, Madrid, Spain) and the Comunidad de Madrid (Spain). Some experiments related to the data shown in Fig.\u00a0\n                      \n                      , as well as the Ki67 (at E18.5) and RC2 results, were performed at the Tata Institute of Fundamental Research following animal protocols approved by the Institution\u2019s Animal Ethics Committee and according to the regulations devised by the Committee for the Purpose of Control and Supervision of Experiments on Animals. Animals were administered food and water ad libitum, and they were housed in strictly controlled environmental conditions: 12\u00a0h light\/dark cycle, 22\u00a0\u00b0C temperature and 44% humidity. All efforts were made to ameliorate the animal\u2019s suffering.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research Involving Animals."}}]}}