Progressive disorganization of paranodal junctions and compact myelin due to loss of DCC expression by oligodendrocytes

Sarah-Jane Bull, Jenea M Bin, Eric Beaumont, Alexandre Boutet, Paul Krimpenfort, Abbas F Sadikot, Timothy E Kennedy

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)9768-78
Number of pages11
JournalJournal of Neuroscience
Volume34
Issue number29
DOIs
Publication statusPublished - 16 Jul 2014

Keywords

  • Animals
  • Axons
  • Cell Count
  • Embryo, Mammalian
  • Estrogen Antagonists
  • Exploratory Behavior
  • Gap Junctions
  • Gene Expression Regulation, Developmental
  • Integrases
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Myelin Proteolipid Protein
  • Myelin Sheath
  • Neural Conduction
  • Oligodendroglia
  • Psychomotor Disorders
  • Ranvier's Nodes
  • Receptors, Cell Surface
  • Tamoxifen
  • Tumor Suppressor Proteins

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