title: MicroRNA-181 promotes synaptogenesis and attenuates axonal outgrowth in cortical neurons.
abstract: MicroRNAs (miRs) are non-coding gene transcripts abundantly expressed in both the developing and adult mammalian brain. They act as important modulators of complex gene regulatory networks during neuronal development and plasticity. miR-181c is highly abundant in cerebellar cortex and its expression is increased in autism patients as well as in an animal model of autism. To systematically identify putative targets of miR-181c, we repressed this miR in growing cortical neurons and found over 70 differentially expressed target genes using transcriptome profiling. Pathway analysis showed that the miR-181c-modulated genes converge on signaling cascades relevant to neurite and synapse developmental processes. To experimentally examine the significance of these data, we inhibited miR-181c during rat cortical neuronal maturation in vitro; this loss-of miR-181c function resulted in enhanced neurite sprouting and reduced synaptogenesis. Collectively, our findings suggest that miR-181c is a modulator of gene networks associated with cortical neuronal maturation.
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Aron
authors.initials: A
authors.lastname: Kos
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Nikkie
authors.initials: N
authors.lastname: Olde Loohuis
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Julia
authors.initials: J
authors.lastname: Meinhardt
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.affiliation: Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Barry B
authors.initials: BB
authors.lastname: Kaplan
authors.affiliation: Department of Molecular Animal Physiology, Radboud University, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Martens
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands. armaz.aschrafi@gmail.com.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands. armaz.aschrafi@gmail.com.|Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. armaz.aschrafi@gmail.com.
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D017209:Apoptosis; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D053263:Gene Regulatory Networks; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: D000070416:Antagomirs; D035683:MicroRNAs; C529100:mirn181 microRNA, mouse; D012313:RNA
keywords: Cortex; Neurodevelopment; Neuronal morphology; Non-coding RNA; Post-transcriptional regulation