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

Nira de la Vega Gallardo, Rosana Penalva, Marie Dittmer , Michelle Naughton, John Falconer, Jill Moffat, Alerie G. de la Fuente , Jose R Hombrebueno, Zhiyong Lin, Bernard Perbal, Rebecca J . Ingram, Emma Evergren, Denise C. Fitzgerald

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2 Citations (Scopus)
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CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3-/- mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.
Original languageEnglish
Pages (from-to)18018-18028
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number30
Publication statusPublished - 10 Jul 2020

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. 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. 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).

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Copyright 2020 Elsevier B.V., All rights reserved.


  • CCN3
  • Myelin
  • OPC
  • Oligodendrocyte
  • Remyelination
  • Gene Expression Regulation
  • Spinal Cord/metabolism
  • Oligodendrocyte Precursor Cells/metabolism
  • Central Nervous System/metabolism
  • Animals
  • Remyelination/genetics
  • Fluorescent Antibody Technique
  • Oligodendroglia/metabolism
  • Nephroblastoma Overexpressed Protein/genetics
  • Mice
  • Myelin Sheath/metabolism
  • Demyelinating Diseases/etiology
  • Brain/metabolism
  • Disease Models, Animal

ASJC Scopus subject areas

  • General


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