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To investigate its pathophysiological contributions, murine models are generated through conditional\n                    <jats:italic>Eftud2<\/jats:italic>\n                    ablation and in utero electroporation of human pathogenic\n                    <jats:italic>EFTUD2<\/jats:italic>\n                    variants into cortical neural stem cells (NSCs). Embryonic NSC\u2010specific\n                    <jats:italic>Eftud2<\/jats:italic>\n                    knockout resulted in cortical disorganization and microcephaly, while pathogenic variants led to significant neuronal loss. Integrative transcriptomic and immunofluorescence analyses revealed that\n                    <jats:italic>Eftud2<\/jats:italic>\n                    deficiency triggers apoptotic pathways, contributing to cortical malformations. Mechanistic studies using RNA co\u2010immunoprecipitation and full\u2010length transcriptome sequencing demonstrated that Eftud2 directly interacts with\n                    <jats:italic>Caspase3<\/jats:italic>\n                    and\n                    <jats:italic>Aifm1<\/jats:italic>\n                    transcripts, regulating their alternative splicing to generate pro\u2010apoptotic isoforms. Splicing assays functionally validated this regulatory mechanism, showing its role in activating cell death pathways and disrupting neurodevelopmental homeostasis. These findings elucidate EFTUD2's critical role in maintaining apoptotic balance during corticogenesis and identify defective splicing regulation as the molecular basis of MFDM. This study provides insights for advancing diagnostic frameworks and therapeutic strategies for neurodevelopmental disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504200","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T08:36:30Z","timestamp":1748680590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EFTUD2 Regulates Cortical Morphogenesis via Modulation of\n                    <i>Caspase\u20103<\/i>\n                    and\n                    <i>Aifm1<\/i>\n                    Splicing Pathways"],"prefix":"10.1002","volume":"12","author":[{"given":"Liping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingze","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghe","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Beijing Institute of Basic Medical Sciences  Beijing 100850 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