title: Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.
abstract: We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the α-subunit (Gαi2) with in utero electroporation caused delayed radial migration of excitatory neurons during corticogenesis, perhaps because of impaired morphology. The migration phenotype was rescued by an RNAi-resistant version of Gαi2. On the other hand, silencing of Gαi2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Gαi2-knockdown mice, they showed defects in social interaction, novelty recognition and active avoidance learning as well as increased anxiety. Subsequently, using whole-exome sequencing analysis, we identified a de novo heterozygous missense mutation (c.680C>T; p.Ala227Val) in the GNAI2 gene encoding Gαi2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Gαi2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders.
authors: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.|Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
authors: Nanako
authors: N
authors: Hamada
authors: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Yutaka
authors: Y
authors: Negishi
authors: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
authors: Makoto
authors: M
authors: Mizuno
authors: Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors: Fuyuki
authors: F
authors: Miya
authors: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Ayako
authors: A
authors: Hattori
authors: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors: Nobuhiko
authors: N
authors: Okamoto
authors: Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
authors: Mitsuhiro
authors: M
authors: Kato
authors: Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors: Tatsuhiko
authors: T
authors: Tsunoda
authors: Department of Neurosurgery, Takatsuki General Hospital, Osaka, Japan.
authors: Mami
authors: M
authors: Yamasaki
authors: Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.|Department of Neurosurgery, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
authors: Yonehiro
authors: Y
authors: Kanemura
authors: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors: Kenjiro
authors: K
authors: Kosaki
authors: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
authors: Hidenori
authors: H
authors: Tabata
authors: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Shinji
authors: S
authors: Saitoh
authors: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.|Department of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Koh-Ichi
authors: KI
authors: Nagata
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D019556:COS Cells; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D054091:Periventricular Nodular Heterotopia / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D051960:GTP-Binding Protein alpha Subunit, Gi2
keywords: GTP-binding protein; Gi2; cortical neuron; corticogenesis; migration; neurodevelopmental disorders