title: Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio.
abstract: Oligodendrocytes produce multi-lamellar myelin membranes that surround axons in the central nervous system (CNS). Preservation and generation of myelin are potential therapeutic targets for dysmyelinating and demyelinating diseases. MicroRNAs (miRNAs) play a vital role in oligodendrocyte differentiation and overall CNS development. miR-124 is a well-conserved neuronal miRNA with important roles in neuronal differentiation and function. miR-124 levels increase following loss of myelin in both human and rodent brains. While the role of neuronal miR-124 in neurogenesis has been established, its effects on axonal outgrowth and oligodendrocytes are not currently known. We therefore explored the possible effect of selective knockdown of miR-124 in Danio rerio using a morpholino-based knockdown approach. No morphological abnormalities or loss of motor neurons were detected despite loss of axonal outgrowth. Morpholino-based knockdown of miR-124 led to reciprocal increases in mRNA levels of target genes that inhibit axonal and dendritic projections. Importantly, loss of miR-124 led to decreased oligodendrocyte cell numbers and myelination of axonal projections in the ventral hindbrain. Taken together, our results add a new dimension to the existing complexity of neuron-glial relationships and highlight the utility of Danio rerio as a model system to investigate such interactions.
authors.affiliation: Department of Biology, BaldwinWallace University, Berea, OH, 44017, USA.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Morris
authors.forename: Anthony
authors.initials: A
authors.lastname: Chomyk
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Nate
authors.initials: N
authors.lastname: Parker
authors.forename: Sadie
authors.initials: S
authors.lastname: Deckard
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
authors.forename: Sanjay W
authors.initials: SW
authors.lastname: Pimplikar
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dutta
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007814:Larva; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology*
chemical_list: D035683:MicroRNAs; D060172:Morpholinos