{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:35:31Z","timestamp":1772998531956,"version":"3.50.1"},"posted":{"date-parts":[[2023,11,30]]},"group-title":"Neuroscience","reference-count":20,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Brain somatic variants in\n                  <jats:italic>SLC35A2<\/jats:italic>\n                  are associated with clinically drug-resistant epilepsy and developmental brain malformations, including mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).\n                  <jats:italic>SLC35A2<\/jats:italic>\n                  encodes a uridine diphosphate galactose translocator that is essential for protein glycosylation; however, the neurodevelopmental mechanisms by which\n                  <jats:italic>SLC35A2<\/jats:italic>\n                  disruption leads to clinical and histopathological features remain unspecified. We hypothesized that focal knockout (KO) or knockdown (KD) of\n                  <jats:italic>Slc35a2<\/jats:italic>\n                  in the developing mouse cortex would disrupt cerebral cortical development through altered neuronal migration and cause changes in network excitability. We used\n                  <jats:italic>in utero<\/jats:italic>\n                  electroporation (IUE) to introduce CRISPR\/Cas9 and targeted guide RNAs or short-hairpin RNAs to achieve\n                  <jats:italic>Slc35a2<\/jats:italic>\n                  KO or KD, respectively, during early corticogenesis. Following\n                  <jats:italic>Slc35a2<\/jats:italic>\n                  KO or KD, we observed disrupted radial migration of transfected neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter.\n                  <jats:italic>Slc35a2<\/jats:italic>\n                  KO in neurons did not induce changes in oligodendrocyte number, suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects. Spontaneous seizures were not observed, but intracranial EEG recordings after focal KO showed a reduced seizure threshold following pentylenetetrazol injection. These results demonstrate that\n                  <jats:italic>Slc35a2<\/jats:italic>\n                  KO or KD\n                  <jats:italic>in vivo<\/jats:italic>\n                  disrupts corticogenesis through altered neuronal migration.\n                <\/jats:p>","DOI":"10.1101\/2023.11.29.569243","type":"posted-content","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T18:15:10Z","timestamp":1701368110000},"source":"Crossref","is-referenced-by-count":2,"title":["Loss of\n                  <i>Slc35a2<\/i>\n                  alters development of the mouse cerebral cortex"],"prefix":"10.64898","author":[{"given":"Soad","family":"Elziny","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahibjot","family":"Sran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyojung","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel R.","family":"Corrigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Ringland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lanier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Lapidus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Foreman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin 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