Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve

Neuron. 2000 Oct;28(1):81-90. doi: 10.1016/s0896-6273(00)00087-8.


It was previously shown that newly formed oligodendrocytes depend on axons for their survival, but the nature of the axon-derived survival signal(s) remained unknown. We show here that neuregulin (NRG) supports the survival of purified oligodendrocytes and aged oligodendrocyte precursor cells (OPCs) but not of young OPCs. We demonstrate that axons promote the survival of purified oligodendrocytes and that this effect is inhibited if NRG is neutralized. In the developing rat optic nerve, we provide evidence that delivery of NRG decreases both normal oligodendrocyte death and the extra oligodendrocyte death induced by nerve transection, whereas neutralization of endogenous NRG increases the normal death. These results suggest that NRG is an axon-associated survival signal for developing oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axotomy
  • COS Cells
  • Cell Count
  • Cell Survival / drug effects
  • Cell Survival / physiology*
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Neuregulin-1 / genetics
  • Neuregulin-1 / metabolism*
  • Neuregulin-1 / pharmacology
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism*
  • Optic Nerve / cytology
  • Optic Nerve / drug effects
  • Optic Nerve / growth & development
  • Optic Nerve / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Transfection


  • Neuregulin-1