title: MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes.
abstract: MicroRNAs (miRs) are small non-coding RNAs that confer robustness to gene networks through post-transcriptional gene regulation. Previously, we identified miR-338 as a modulator of axonal outgrowth in sympathetic neurons. In the current study, we examined the role of miR-338 in the development of cortical neurons and uncovered its downstream mRNA targets. Long-term inhibition of miR-338 during neuronal differentiation resulted in reduced dendritic complexity and altered dendritic spine morphology. Furthermore, monitoring axon outgrowth in cortical cells revealed that miR-338 overexpression decreased, whereas inhibition of miR-338 increased axonal length. To identify gene targets mediating the observed phenotype, we inhibited miR-338 in cortical neurons and performed whole-transcriptome analysis. Pathway analysis revealed that miR-338 modulates a subset of transcripts involved in the axonal guidance machinery by means of direct and indirect gene targeting. Collectively, our results implicate miR-338 as a novel regulator of cortical neuronal maturation by fine-tuning the expression of gene networks governing cortical outgrowth.
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: Teun
authors.initials: T
authors.lastname: Klein-Gunnewiek
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.|Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: Nikkie F M Olde
authors.initials: NFMO
authors.lastname: 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.|Department of Human Genetics, Radboud university medical center, 6500 HB, 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, Maryland, 20892, USA.
authors.forename: Barry B
authors.initials: BB
authors.lastname: Kaplan
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.|Department of Molecular Animal Physiology, Radboud University, Nijmegen, The Netherlands.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Martens
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.|Department of Molecular Animal Physiology, Radboud University, Nijmegen, The Netherlands.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Kolk
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands. Armaz.aschrafi@nih.gov.|Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, 20892, USA. Armaz.aschrafi@nih.gov.
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000235:genetics*; D001483:Base Sequence; D002540:Cerebral Cortex / Q000166:cytology*; D049229:Dendritic Spines / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D035683:MicroRNAs; D011971:Receptors, Immunologic; C573089:MIRN338 microRNA, rat; C516057:Robo2 protein, rat; D000097905:Roundabout Proteins
keywords: Cortex; MicroRNA; Neurite development; Neurodevelopment; Robo2