TY - JOUR TI - miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6 AU - Franzoni, Eleonora AU - Booker, Sam A AU - Parthasarathy, Srinivas AU - Rehfeld, Frederick AU - Grosser, Sabine AU - Srivatsa, Swathi AU - Fuchs, Heiko R AU - Tarabykin, Victor AU - Vida, Imre AU - Wulczyn, F Gregory A2 - Polleux, Franck VL - 4 PY - 2015 DA - 2015/01/03 SP - e04263 C1 - eLife 2015;4:e04263 DO - 10.7554/eLife.04263 UR - https://doi.org/10.7554/eLife.04263 AB - 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 Börjeson-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. KW - Börjeson-Forssman-Lehmann syndrome KW - cortical development KW - developmental timing KW - post-translational gene regulation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -