title: MicroRNAs contribute to postnatal development of laminar differences and neuronal subtypes in the rat medial entorhinal cortex.
abstract: The medial entorhinal cortex (MEC) is important in spatial navigation and memory formation and its layers have distinct neuronal subtypes, connectivity, spatial properties, and disease susceptibility. As little is known about the molecular basis for the development of these laminar differences, we analyzed microRNA (miRNA) and messenger RNA (mRNA) expression differences between rat MEC layer II and layers III-VI during postnatal development. We identified layer and age-specific regulation of gene expression by miRNAs, which included processes related to neuron specialization and locomotor behavior. Further analyses by retrograde labeling and expression profiling of layer II stellate neurons and in situ hybridization revealed that the miRNA most up-regulated in layer II, miR-143, was enriched in stellate neurons, whereas the miRNA most up-regulated in deep layers, miR-219-5p, was expressed in ependymal cells, oligodendrocytes and glia. Bioinformatics analyses of predicted mRNA targets with negatively correlated expression patterns to miR-143 found that miR-143 likely regulates the Lmo4 gene, which is known to influence hippocampal-based spatial learning.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Lene C
authors.initials: LC
authors.lastname: Olsen
authors.affiliation: Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University for Science and Technology, Trondheim, Norway.
authors.forename: Kally C
authors.initials: KC
authors.lastname: O'Reilly
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Nina B
authors.initials: NB
authors.lastname: Liabakk
authors.affiliation: Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University for Science and Technology, Trondheim, Norway.
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. pal.satrom@ntnu.no.|Department of Computer and Information Science, Norwegian University for Science and Technology, Trondheim, Norway. pal.satrom@ntnu.no.|Bioinformatics core facility-BioCore, Norwegian University of Science and Technology, Trondheim, Norway. pal.satrom@ntnu.no.
authors.forename: Pål
authors.identifier: http://orcid.org/0000-0001-8142-7441
authors.initials: P
authors.lastname: Sætrom
mesh_terms: D000367:Age Factors; D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D016000:Cluster Analysis; D019295:Computational Biology; D018728:Entorhinal Cortex / Q000166:cytology* / Q000254:growth & development*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D063990:Gene Ontology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats
chemical_list: D035683:MicroRNAs
keywords: Brain development; Medial entorhinal cortex; MiRNA; Stellate neurons