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Role of a heterotrimeric G‐protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability
Author(s) -
Hamada Nanako,
Negishi Yutaka,
Mizuno Makoto,
Miya Fuyuki,
Hattori Ayako,
Okamoto Nobuhiko,
Kato Mitsuhiro,
Tsunoda Tatsuhiko,
Yamasaki Mami,
Kanemura Yonehiro,
Kosaki Kenjiro,
Tabata Hidenori,
Saitoh Shinji,
Nagata Kohichi
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13878
Subject(s) - corticogenesis , heterotrimeric g protein , intellectual disability , neuronal migration , medicine , neuroscience , psychology , biology , psychiatry , g protein , genetics , receptor , embryonic stem cell , gene
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 RNA i‐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 GNAI 2 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.