Dorsally-derived oligodendrocytes in the spinal cord contribute to axonal myelination during development and remyelination following focal demyelination

Glia. 2011 Nov;59(11):1612-21. doi: 10.1002/glia.21203. Epub 2011 Jun 27.

Abstract

In the developing spinal cord, the majority of oligodendrocytes are derived from the ventral ventricular zone. Several recent studies suggested that a small number of oligodendrocyte precursor cells (OPCs) can also be generated in the dorsal spinal cord. However, it is not clear whether these dorsal oligodendrocyte precursor cells participate in myelination and remyelination. To investigate the fate and potential function of these dorsally-derived oligodendrocytes (dOLs) in the adult spinal cord, Cre-lox genetic fate mapping in transgenic mice was employed. We used the Pax3(Cre) knock-in mouse to drive Cre expression in the entire dorsal epithelium and the Rosa26-lacZ or Z/EG reporter line to trace their spatial distribution and population dynamics in the spinal cord. The dorsal OPCs generated from the Pax3-expressing domains migrate into all regions of spinal cord and subsequently undergo terminal differentiation and axonal myelination. In response to a focal demyelination injury, a large number of newly differentiated oligodendrocytes originated from dOLs, suggesting that dOLs may provide an important source of OPCs for axonal remyelination in multiple sclerosis or spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Axons / physiology*
  • Bromodeoxyuridine
  • Cell Differentiation / physiology
  • Data Interpretation, Statistical
  • Demyelinating Diseases / pathology*
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Lac Operon / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Electron
  • Myelin Sheath / physiology*
  • Neural Stem Cells
  • Oligodendroglia / physiology*
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / biosynthesis
  • Paired Box Transcription Factors / genetics
  • Spinal Cord / cytology*
  • Spinal Cord / growth & development
  • Spinal Cord / physiology
  • Spinal Cord Injuries / pathology

Substances

  • Antimetabolites
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pax3 protein, mouse
  • Green Fluorescent Proteins
  • Bromodeoxyuridine