miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6
- Charité-Universitätsmedizin Berlin, Germany
- Heinrich Heine University, Germany
Abstract
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.
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Ethics
Animal experimentation: All experiments were conducted according to the European and German laws, in conformance with the Animal Welfare Act and the European legislative Directives 86/609/EEC 2010/63/EU from 2010 on as updated in 2013. The animal welfare committee of the Charité, Berlin, approved and supervised the experiments performed under the experimental license number T01012/11. All surgery was performed using Isofluran as anesthetic and Temgesic® for analgesia as required to minimize suffering.
Copyright
© 2015, Franzoni et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6
eLife 4:e04263.
https://doi.org/10.7554/eLife.04263
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