title: Tcf4 Controls Neuronal Migration of the Cerebral Cortex through Regulation of Bmp7.
abstract: Background:Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear.Results:Here, we report thatTcf4is expressed in the developing cerebral cortex.In uterosuppression ofTcf4arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown ofTcf4impaired leading process formation. Furthermore, Bone Morphogenetic Protein 7 (Bmp7) is upregulated inTcf4-deficient neurons.In vivogain of function and rescue experiments demonstrated that Bmp7 is the major downstream effector ofTcf4required for neuronal migration.Conclusion:Thus, we have uncovered a newTcf4/Bmp7-dependent mechanism underlying neuronal migration, and provide insights into the pathogenesis of neurodevelopmental disorders.
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, BeijingChina.
authors.forename: Tianda
authors.initials: T
authors.lastname: Chen
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Academy for Advanced Interdisciplinary Studies, Peking UniversityBeijing, China; Peking-Tsinghua Center for Life Sciences, Peking UniversityBeijing, China.
authors.forename: Qinwei
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, BeijingChina.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, BeijingChina.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, BeijingChina.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Institute of Mental Health, Peking University Sixth Hospital, BeijingChina; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, BeijingChina; Peking-Tsinghua Center for Life Sciences, Peking UniversityBeijing, China; PKU-IDG/McGovern Institute for Brain Research, Peking UniversityBeijing, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
keywords: Bmp7; TCF4; brain development; neuronal migration; schizophrenia