title: Progressive disorganization of paranodal junctions and compact myelin due to loss of DCC expression by oligodendrocytes.
abstract: Paranodal axoglial junctions are critical for maintaining the segregation of axonal domains along myelinated axons; however, the proteins required to organize and maintain this structure are not fully understood. Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC) are proteins enriched at paranodes that are expressed by neurons and oligodendrocytes. To identify the specific function of DCC expressed by oligodendrocytes in vivo, we selectively eliminated DCC from mature myelinating oligodendrocytes using an inducible cre regulated by the proteolipid protein promoter. We demonstrate that DCC deletion results in progressive disruption of the organization of axonal domains, myelin ultrastructure, and myelin protein composition. Conditional DCC knock-out mice develop balance and coordination deficits and exhibit decreased conduction velocity. We conclude that DCC expression by oligodendrocytes is required for the maintenance and stability of myelin in vivo, which is essential for proper signal conduction in the CNS.
authors.affiliation: Department of Neurology and Neurosurgery and.
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Bull
authors.affiliation: Department of Neurology and Neurosurgery and.
authors.forename: Jenea M
authors.initials: JM
authors.lastname: Bin
authors.affiliation: Département de Chirurgie, Université de Montréal, Montreal, Quebec, Canada, H3C 3J7, and.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0003-2907-7768
authors.initials: E
authors.lastname: Beaumont
authors.affiliation: Cone Laboratory, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada, H3A 2B4.
authors.forename: Alexandre
authors.identifier: http://orcid.org/0000-0001-6942-5195
authors.initials: A
authors.lastname: Boutet
authors.affiliation: Department of Molecular Genetics, Cancer Genomics Centre, Centre for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Krimpenfort
authors.affiliation: Cone Laboratory, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada, H3A 2B4.
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Sadikot
authors.affiliation: Department of Neurology and Neurosurgery and timothy.kennedy@mcgill.ca.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002452:Cell Count; D000075389:DCC Receptor; D004622:Embryo, Mammalian; D004965:Estrogen Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D011596:Psychomotor Disorders / Q000235:genetics; D011901:Ranvier's Nodes / Q000378:metabolism / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D004965:Estrogen Antagonists; D018991:Myelin Proteolipid Protein; C047516:Plp1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: DCC; caspr; myelin; netrin; oligodendrocyte; paranode