| First Author | Franzoni E | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 25556700 | Mgi Jnum | J:229060 |
| Mgi Id | MGI:5750284 | Doi | 10.7554/eLife.04263 |
| Citation | Franzoni E, et al. (2015) miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6. Elife 4 |
| abstractText | miR-128, a brain-enriched microRNA, has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed. We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adult stem cell niches. Whereas premature miR-128 expression in progenitors for upper layer neurons leads to impaired neuronal migration and inappropriate branching, sponge-mediated inhibition results in overmigration. Within the upper layers, premature miR-128 expression reduces the complexity of dendritic arborization, associated with altered electrophysiological properties. We show that Phf6, a gene mutated in the cognitive disorder Borjeson-Forssman-Lehmann syndrome, is an important regulatory target for miR-128. Restoring PHF6 expression counteracts the deleterious effect of miR-128 on neuronal migration, outgrowth and intrinsic physiological properties. Our results place miR-128 upstream of PHF6 in a pathway vital for cortical lamination as well as for the development of neuronal morphology and intrinsic excitability. |
