Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination
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Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination. / de la Vega Gallardo, Nira ; Penalva, Rosana ; Dittmer , Marie ; Naughton, Michelle ; Falconer, John ; Moffat, Jill ; de la Fuente , Alerie G.; Romero, Jose; Lin, Zhiyong; Perbal, Bernard ; Ingram, Rebecca J .; Evergren, Emma ; Fitzgerald, Denise C.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 30, 10.07.2020, p. 18018-18028.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination
AU - de la Vega Gallardo, Nira
AU - Penalva, Rosana
AU - Dittmer , Marie
AU - Naughton, Michelle
AU - Falconer, John
AU - Moffat, Jill
AU - de la Fuente , Alerie G.
AU - Romero, Jose
AU - Lin, Zhiyong
AU - Perbal, Bernard
AU - Ingram, Rebecca J .
AU - Evergren, Emma
AU - Fitzgerald, Denise C.
N1 - 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: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/10
Y1 - 2020/7/10
N2 - 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.
AB - 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.
KW - CCN3
KW - Myelin
KW - OPC
KW - Oligodendrocyte
KW - Remyelination
KW - Gene Expression Regulation
KW - Spinal Cord/metabolism
KW - Oligodendrocyte Precursor Cells/metabolism
KW - Central Nervous System/metabolism
KW - Animals
KW - Remyelination/genetics
KW - Fluorescent Antibody Technique
KW - Oligodendroglia/metabolism
KW - Nephroblastoma Overexpressed Protein/genetics
KW - Mice
KW - Myelin Sheath/metabolism
KW - Demyelinating Diseases/etiology
KW - Brain/metabolism
KW - Disease Models, Animal
UR - http://www.scopus.com/inward/record.url?scp=85088879787&partnerID=8YFLogxK
U2 - 10.1073/pnas.1922089117
DO - 10.1073/pnas.1922089117
M3 - Article
C2 - 32651278
VL - 117
SP - 18018
EP - 18028
JO - Proceedings of the National Academy of Sciences
JF - Proceedings of the National Academy of Sciences
SN - 1091-6490
IS - 30
ER -