NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar-bipolar transition.
Abnormalities during brain development are tightly linked several psychiatric disorders. Mutations in NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2) are responsible for schizophrenia, bipolar disorder and Parkinson׳s disease. However, the function of NDUFV2 during brain development remains unclear. Here we reported that ndufv2 is expressed in the developing cerebral cortex. In utero suppression of ndufv2 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. ndufv2 inhibition did not affect radial glia scaffold, progenitor cells or neurons survival. However, the loss of ndufv2 impairs neuronal multipolar-bipolar transition in vivo and polarization in vitro. Moreover, ndufv2 affected actin cytoskeleton and tubulin stabilization in cortical neurons. Overall, our findings establish a new NDUFV2 dependent mechanism underlying neuronal migration and psychiatric disorders.
Institute of Mental Health, The Sixth Hospital, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing 100191, China. Electronic address: Tiandachen@bjmu.edu.cn.
Tianda
T
Chen
Academy for Advanced Interdisciplinary Studies, Peking University, China; Peking-Tsinghua Center for Life Sciences, Peking University, China.
Qinwei
Q
Wu
Institute of Mental Health, The Sixth Hospital, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing 100191, China.
Yang
Y
Zhang
Institute of Mental Health, The Sixth Hospital, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China. Electronic address: daizhang@bjmu.edu.cn.
Dai
D
Zhang
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018274:Electroporation; D004622:Embryo, Mammalian; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D009245:NADH Dehydrogenase; D053148:Caspase 3
Developing cerebral cortex; In utero Electroporation; NDUFV2; Neuronal migration