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Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA\u201034a (miR\u201034a) among the most upregulated miRs in tubers. Here, we characterised miR\u201034a expression in tubers with the focus on the early brain development and assessed the regulation of mTORC1 pathway and corticogenesis by miR\u201034a.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed the expression of miR\u201034a in resected cortical tubers (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a037) compared with autopsy\u2010derived control tissue (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a027). The effect of miR\u201034a overexpression on corticogenesis was assessed in mice at E18. The regulation of the mTORC1 pathway and the expression of the bioinformatically predicted target genes were assessed in primary astrocyte cultures from three patients with TSC and in SH\u2010SY5Y cells following miR\u201034a transfection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The peak of miR\u201034a overexpression in tubers was observed during infancy, concomitant with the presence of pathological markers, particularly in giant cells and dysmorphic neurons. miR\u201034a was also strongly expressed in foetal TSC cortex. Overexpression of miR\u201034a in mouse embryos decreased the percentage of cells migrated to the cortical plate. The transfection of miR\u201034a mimic in TSC astrocytes negatively regulated mTORC1 and decreased the expression of the target genes RAS related (\n                      <jats:italic>RRAS<\/jats:italic>\n                      ) and\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MicroRNA\u201034a is most highly overexpressed in tubers during foetal and early postnatal brain development. miR\u201034a can negatively regulate mTORC1; however, it may also contribute to abnormal corticogenesis in TSC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12717","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T02:35:42Z","timestamp":1620095742000},"page":"796-811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MicroRNA\u201034a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-6282","authenticated-orcid":false,"given":"Anatoly","family":"Korotkov","sequence":"first","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam Suk","family":"Sim","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology  Daejeon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Luinenburg","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper J.","family":"Anink","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackelien","family":"van Scheppingen","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"},{"name":"Department of Neuroimmunology Netherlands Institute for Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-3697","authenticated-orcid":false,"given":"Till S.","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-4240","authenticated-orcid":false,"given":"Anika","family":"Bongaarts","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology Amsterdam UMC University of Amsterdam Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4842-0659","authenticated-orcid":false,"given":"Diede W. 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