title: Cdon, a cell surface protein, mediates oligodendrocyte differentiation and myelination.
abstract: During central nervous system development, oligodendrocyte progenitors (OLPs) establish multiple branched processes and axonal contacts to initiate myelination. A complete understanding of the molecular signals implicated in cell surface interaction to initiate myelination/remyelination is currently lacking. The objective of our study was to assess whether Cdon, a cell surface protein that was shown to participate in muscle and neuron cell development, is involved in oligodendrocyte (OLG) differentiation and myelination. Here, we demonstrate that endogenous Cdon protein is expressed in OLPs, increasing in the early differentiation stages and decreasing in mature OLGs. Immunocytochemistry of endogenous Cdon showed localization on both OLG cell membranes and cellular processes exhibiting puncta- or varicosity-like structures. Cdon knockdown with siRNA decreased protein levels by 62% as well as two myelin-specific proteins, MBP and MAG. Conversely, overexpression of full-length rat Cdon increased myelin proteins in OLGs. The complexity of OLGs branching and contact point numbers with axons were also increased in Cdon overexpressing cells growing alone or in coculture with dorsal root ganglion neurons (DRGNs). Furthermore, myelination of DRGNs was decreased when OLPs were transfected with Cdon siRNA. Altogether, our results suggest that Cdon participates in OLG differentiation and myelination, most likely in the initial stages of development.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada, H3G 1Y6.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada, H3G 1Y6.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Almazan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology
chemical_list: C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D004676:Myelin Basic Protein; D009185:Myelin Proteins
keywords: Cdon; DRGN; central nervous system; myelin; oligodendrocyte progenitor