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.
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Acknowledgments
The authors would like to thank Dr. Stephen Stohlman for his comments and Dr. Christopher Nelson for manuscript editing.
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The work was supported by a Grant from the National Multiple Sclerosis Society, USA (RG-4280 to RD), and Baldwin Wallace University Faculty Development award (JKM).
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Morris, J.K., Chomyk, A., Song, P. et al. Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio . Invert Neurosci 15, 4 (2015). https://doi.org/10.1007/s10158-015-0180-1
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DOI: https://doi.org/10.1007/s10158-015-0180-1