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Author Notes:

d.fitzgerald@qub.ac.uk

Author contributions: N.d.l.V.G., R.P., M.N., A.G.d.l.F., Z.L., B.P., R.J.I., and D.C.F. designed research; N.d.l.V.G., R.P., M.D., J.F., J.M., J.R.H., and E.E. performed research; N.d.l.V.G. and M.D. analyzed data; N.d.l.V.G. and D.C.F. wrote the paper; R.P., M.N., A.G.d.l.F., Z.L., B.P., and R.J.I. provided advice on experimental design and interpretation and contributed toward writing the manuscript via suggested edits; M.D., J.R.H., and E.E. contributed toward writing the manuscript via suggested edits; and D.C.F. provided advice on experimental design and interpretation and oversaw the study.

We thank Prof. Anna Williams and her team for kindly providing us with the ImageJ macro used to analyse brain slice images in this study. We thank Anna Magennis for technical support and Rachel Jayne Gillis and Sarah Collis for cell quantification. We also thank QUB Biological Services Unit and the advanced imaging unit staff for their help and advice, particularly Andrena Millar and Dr. Ileana Micu. We thank Dr. Yvonne Dombrowski’s laboratory, Dr. Liza Colhoun, and WWIEM immunology laboratory groups for their advice and guidance through the course of this study.

The authors declare no competing interest.

Subjects:

Research Funding:

This work was supported by Biotechnology and Biological Sciences Research Council Grant BB/J01026X/1 (to D.C.F.), Wellcome Trust Grant 110138/Z/15/Z (to D.C.F.), and studentship support from the Department for the Economy (Northern Ireland).

Keywords:

  • CCN3
  • myelin
  • oligodendrocyte
  • OPC
  • remyelination

Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination

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Journal Title:

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Volume:

Volume 117, Number 30

Publisher:

, Pages 18018-18028

Type of Work:

Article | Final Publisher PDF

Abstract:

Remyelination is a natural regenerative process driven by oligodendrocytes that occurs following myelin damage. Understanding this process holds therapeutic value for demyelinating diseases such as multiple sclerosis, in which remyelination can fail. CCN3 is a matricellular protein previously reported to enhance oligodendrocyte progenitor differentiation and myelination in vitro and ex vivo. Here, we show that despite extensive and dynamic expression in the murine CNS in homeostasis and following toxin-induced myelin damage, CCN3 is not required for myelination or remyelination in vivo. Yet, the anatomically distinct expression pattern suggests unidentified roles of CCN3 in a range of neurological processes. This investigation provides a framework for future investigations of the expression and role of CCN proteins in the CNS.

Copyright information:

© 2020 the Author(s). Published by PNAS.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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