Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability

Nanako Hamada, Yutaka Negishi, Makoto Mizuno, Fuyuki Miya, Ayako Hattori, Nobuhiko Okamoto, Mitsuhiro Kato, Tatsuhiko Tsunoda, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki, Hidenori Tabata, Shinji Saitoh, Koh Ichi Nagata

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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. (Figure presented.).

Original languageEnglish
Pages (from-to)82-95
Number of pages14
JournalJournal of Neurochemistry
Volume140
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Keywords

  • GTP-binding protein
  • Gi2
  • cortical neuron
  • corticogenesis
  • migration
  • neurodevelopmental disorders

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Hamada, N., Negishi, Y., Mizuno, M., Miya, F., Hattori, A., Okamoto, N., Kato, M., Tsunoda, T., Yamasaki, M., Kanemura, Y., Kosaki, K., Tabata, H., Saitoh, S., & Nagata, K. I. (2017). Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability. Journal of Neurochemistry, 140(1), 82-95. https://doi.org/10.1111/jnc.13878