| First Author | Hamada N | Year | 2017 |
| Journal | J Neurochem | Volume | 140 |
| Issue | 1 | Pages | 82-95 |
| PubMed ID | 27787898 | Mgi Jnum | J:238431 |
| Mgi Id | MGI:5819320 | Doi | 10.1111/jnc.13878 |
| Citation | Hamada N, et al. (2017) Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability. J Neurochem 140(1):82-95 |
| abstractText | We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the alpha-subunit (Galphai2) 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 Galphai2. On the other hand, silencing of Galphai2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Galphai2-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 Galphai2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Galphai2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders. |
