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These mice present with neuroanatomical anomalies and microcephaly associated with behavioral deficiencies and susceptibility to epilepsy, correlating with the described human phenotype. Using the flexibility of this model, we investigated RosaCre-, NestinCre- and NexCre-driven expression of the mutation to dissect the pathophysiological mechanisms underlying neurodevelopmental cortical abnormalities. We show that the expression of the p.His321Asp pathogenic variant increases apoptosis and causes abnormal multipolar to bipolar transition in newborn neurons, providing therefore insights to better understand cortical organization and brain growth defects that characterize KIF2A-related human disorders. We further demonstrate that the observed cellular phenotypes are likely to be linked to deficiency in the microtubule depolymerizing function of KIF2A.<\/jats:p>","DOI":"10.1093\/hmg\/ddz316","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T15:11:22Z","timestamp":1576854682000},"page":"766-784","source":"Crossref","is-referenced-by-count":29,"title":["Conditional switching of KIF2A mutation provides new insights into cortical malformation pathogeny"],"prefix":"10.1093","volume":"29","author":[{"given":"Johan G","family":"Gilet","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, 67400 Illkirch, France"},{"name":"CNRS UMR 7104, 67400 Illkirch, France"},{"name":"INSERM U1258, 67400 Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, 67400 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina 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