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

• Type of Material: Article
• Authors: Nira de la Vega Gallardo, Queen’s University Belfast; Rosana Penalva, Queen’s University Belfast; Marie Dittmer, Queen’s University Belfast; Michelle Naughton, Queen’s University Belfast; John Falconer, Queen’s University Belfast; Jill Moffat, Queen’s University Belfast; Alerie G. de la Fuente, Queen’s University Belfast; Jose R. Hombrebueno, University of Birmingham; Zhiyong Lin, Emory University; Bernard Perbal, University of Birmingham; Rebecca J. Ingram, Queen’s University Belfast; Emma Evergren, Queen’s University Belfast; Denise C. Fitzgerald, Queen’s University Belfast
• Language: English
• Date: 2020-07-28
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2020 the Author(s). Published by PNAS.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1922089117
• Title of Journal or Parent Work: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• Volume: 117
• Issue: 30
• Start Page: 18018
• End Page: 18028
• Grant/Funding Information: 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: remyelination; oligodendrocyte; myelin; CCN3; OPC
• Research Categories: Biology, Neuroscience; Health Sciences, Oncology

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.