| First Author | Hamada N | Year | 2021 |
| Journal | J Neurochem | Volume | 157 |
| Issue | 4 | Pages | 1167-1181 |
| PubMed ID | 33025585 | Mgi Jnum | J:308606 |
| Mgi Id | MGI:6730207 | Doi | 10.1111/jnc.15205 |
| Citation | Hamada N, et al. (2021) Heterotrimeric G-protein, Gi1, is involved in the regulation of proliferation, neuronal migration, and dendrite morphology during cortical development in vivo. J Neurochem 157(4):1167-1181 |
| abstractText | Heterotrimeric G-proteins are composed of alpha, beta, and gamma subunits, and function as signal transducers. Critical roles of the alpha-subunits of Gi/o family heterotrimeric G-proteins, Galphai2, and Galphao1, have so far been reported in brain development and neurodevelopmental disorders. In this study, we tried to clarify the role of Galphai1, alpha-subunit of another Gi/o family member Gi1, during corticogenesis, based on the recent identification of its gene abnormalities in neurodevelopmental disorders. In western blot analyses, Galphai1 was found to be expressed in mouse brain in a developmental stage-dependent manner. Morphological analyses revealed that Galphai1 was broadly distributed in cerebral cortex with relatively high expression in the ventricular zone (VZ) at embryonic day (E) 14. Meanwhile, Galphai1 was enriched in membrane area of yet unidentified early mitotic cells in the VZ and the marginal zone at E14. Acute knockdown of Galphai1 with in utero electroporation in cerebral cortex caused cell cycle elongation of the neural progenitor cells and promoted their cell cycle exit. Galphai1-deficient cortical neurons also exhibited delayed radial migration during corticogenesis, with abnormally elongated leading processes and hampered nucleokinesis. In addition, silencing of Galphai1 prevented basal dendrite development. The migration and dendritic phenotypes were at least partially rescued by an RNAi-resistant version of Galphai1. Collectively, these results strongly suggest a crucial role of Gi1 in cortical development, and disturbance of its function may cause deficits in synaptic network formation, leading to neurodevelopmental disorders. |
