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In this study, we report six novel cases of patients affected by BBSOAS (Boonstra\u2010Bosch\u2010Schaff optic atrophy syndrome), a newly emerging rare neurodevelopmental disorder, caused by loss\u2010of\u2010function mutations of the transcriptional regulator\n                    <jats:italic>NR2F1<\/jats:italic>\n                    . Young patients with\n                    <jats:italic>NR2F1<\/jats:italic>\n                    haploinsufficiency display mild to moderate intellectual disability and show reproducible polymicrogyria\u2010like brain malformations in the parietal and occipital cortex. Using a recently established BBSOAS mouse model, we found that\n                    <jats:italic>Nr2f1<\/jats:italic>\n                    regionally controls long\u2010term self\u2010renewal of neural progenitor cells via modulation of cell cycle genes and key cortical development master genes, such as\n                    <jats:italic>Pax6<\/jats:italic>\n                    . In the human fetal cortex, distinct NR2F1 expression levels encompass gyri and sulci and correlate with local degrees of neurogenic activity. In addition, reduced NR2F1 levels in cerebral organoids affect neurogenesis and PAX6 expression. We propose\n                    <jats:italic>NR2F1<\/jats:italic>\n                    as an area\u2010specific regulator of mouse and human brain morphology and a novel causative gene of abnormal gyrification.\n                  <\/jats:p>","DOI":"10.15252\/embj.2019104163","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T15:47:30Z","timestamp":1591112850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-4974","authenticated-orcid":false,"given":"Michele","family":"Bertacchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lisa","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Loubat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Tran Mau\u2010Them","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Khau van Kien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Perrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Devillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Sorlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-6303","authenticated-orcid":false,"given":"Paul","family":"Kuentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Philippe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Garde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-3697","authenticated-orcid":false,"given":"Rossella","family":"Di Giaimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Oliviero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4539-9038","authenticated-orcid":false,"given":"Silvia","family":"Cappello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovico","family":"D'Incerti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Frassoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7105-2957","authenticated-orcid":false,"given":"Mich\u00e8le","family":"Studer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"BFEMBJ2019104163_CR1","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.1242\/dev.068031","volume":"138","author":"C Alfano","year":"2011","unstructured":"Alfano C, Viola L, Heng JI\u2010T, Pirozzi M, Clarkson M, Flore G, De Maio A, Schedl A, Guillemot F, Studer M (2011) COUP\u2010TFI promotes radial\u00a0migration and proper morphology of callosal projection neurons\u00a0by repressing Rnd2 expression. 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