Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio

• Published in: Invertebrate neuroscience 2015-09, Vol.15 (3), p.4-4, Article 4
• Main Authors: Morris, Jacqueline K., Chomyk, Anthony, Song, Ping, Parker, Nate, Deckard, Sadie, Trapp, Bruce D., Pimplikar, Sanjay W., Dutta, Ranjan
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Biomedical and Life Sciences; Biomedicine; Cell Biology; Central nervous system; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Invertebrates; Larva; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Medicine; Morpholinos - pharmacology; Neurobiology; Neurosciences; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Original Paper; Zebrafish - anatomy & histology
• ISSN: 1354-2516; 1439-1104
• DOI: 10.1007/s10158-015-0180-1

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.