Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination

J Neurosci. 2006 Jul 19;26(29):7665-73. doi: 10.1523/JNEUROSCI.0444-06.2006.

Abstract

Previous reports, including transplantation experiments using dominant-negative inhibition of beta1-integrin signaling in oligodendrocyte progenitor cells, suggested that beta1-integrin signaling is required for myelination. Here, we test this hypothesis using conditional ablation of the beta1-integrin gene in oligodendroglial cells during the development of the CNS. This approach allowed us to study oligodendroglial beta1-integrin signaling in the physiological environment of the CNS, circumventing the potential drawbacks of a dominant-negative approach. We found that beta1-integrin signaling has a much more limited role than previously expected. Although it was involved in stage-specific oligodendrocyte cell survival, beta1-integrin signaling was not required for axon ensheathment and myelination per se. We also found that, in the spinal cord, remyelination occurred normally in the absence of beta1-integrin. We conclude that, although beta1-integrin may still contribute to other aspects of oligodendrocyte biology, it is not essential for myelination and remyelination in the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Axons / physiology
  • Cell Survival
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / growth & development
  • Central Nervous System / physiology*
  • Cerebellum / physiology
  • Corpus Callosum / metabolism
  • Corpus Callosum / physiology
  • Gene Deletion
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Mice
  • Mice, Knockout
  • Myelin Sheath / physiology*
  • Oligodendroglia / metabolism
  • Oligodendroglia / physiology*
  • Optic Nerve / metabolism
  • Optic Nerve / physiology
  • Signal Transduction / physiology*
  • Spinal Cord / metabolism
  • Spinal Cord / physiology

Substances

  • Integrin beta1