A Subpopulation of Foxj1-Expressing, Nonmyelinating Schwann Cells of the Peripheral Nervous System Contribute to Schwann Cell Remyelination in the Central Nervous System.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Society for Neuroscience
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Ma, D., Wang, B., Zawadzka, M., Gonzalez, G., Wu, Z., Yu, B., Rawlins, E., et al. (2018). A Subpopulation of Foxj1-Expressing, Nonmyelinating Schwann Cells of the Peripheral Nervous System Contribute to Schwann Cell Remyelination in the Central Nervous System.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 38 (43), 9228-9239. https://doi.org/10.1523/jneurosci.0585-18.2018
New myelin sheaths can be restored to demyelinated axons in a spontaneous regenerative process called remyelination. In general, new myelin sheaths are made by oligodendrocytes newly generated from a widespread population of adult CNS progenitors called oligodendrocyte progenitor cells (OPCs). New myelin in CNS remyelination in both experimental models and clinical disease can also be generated by Schwann cells, the myelin forming cells of the peripheral nervous system. Fate mapping studies have shown that Schwann cells contributing to remyelination in the CNS are often derived from OPCs, and appear not to be derived from myelinating Schwann cells from the PNS. In this study we address whether CNS remyelinating Schwann cells can also be generated from PNS derived cells other than myelinating Schwann cells. Using a genetic fate mapping approach, we have found that a sub-population of non-myelinating Schwann cells identified by the expression of the transcription factor foxj1 also contribute to CNS Schwann cell remyelination, as well as to remyelination in the peripheral nervous system. We also find the ependymal cells lining the central canal of the spinal cord, which also express foxj1, do not generate cells that contribute to CNS remyelination. These findings therefore identify a previously unrecognised population of PNS glia that can participate in the regeneration of new myelin sheaths following CNS demyelination.
Central Nervous System, Spinal Cord, Myelin Sheath, Schwann Cells, Peripheral Nervous System, Sciatic Nerve, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Gene Expression, Female, Male, Forkhead Transcription Factors, Remyelination
This work is funded by grants from the UK Multiple Sclerosis Society (941), the Medical Research Council (MR/M010531/1), the Royal Society (NA150482), the Adelson Medical Research Foundation, and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. B.W received funding from the Guangzhou City Overseas Study and Research Scheme. We would like to thank Professor W.D. Richardson for providing PDGFRa-CreERT2 and Sox10iCre lines. Daniel Morrison assisted with tissue processing for electron microscopy
External DOI: https://doi.org/10.1523/jneurosci.0585-18.2018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284740
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Licence URL: https://creativecommons.org/licenses/by/4.0/