GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors

Neuron. 1996 Aug;17(2):229-43. doi: 10.1016/s0896-6273(00)80155-5.


We show that GGF/neuregulin is a mitogen for prooligodendrocytes (O4+/O1- cells), oligodendrocytes (O4+/O1+ cells), and type-2 astrocytes. Heregulin beta 1, another neuregulin isoform, is also mitogenic. The proliferative effect of glial growth factor (GGF) does not require, but is greatly potentiated by, serum factors. GGF also promotes the survival of pro-oligodendrocytes under serum-free conditions. High levels of GGF reversibly inhibit the differentiation and lineage commitment of oligodendrocyte progenitors and, in differentiated cultures, result in loss of O1 and myelin basic protein expression. All three erbB receptors are expressed by progenitors and are activated by GGF; the relative abundance of these receptors changes during differentiation. Finally, cortical neurons release a soluble mitogen for pro-oligodendrocytes that is specifically blocked by antibodies to GGF. These results implicate the neuregulins in the neuronal regulation of oligodendrocyte progenitor proliferation, survival, and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Lineage / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured / cytology
  • Cerebral Cortex / cytology
  • Gene Expression Regulation
  • Glycoproteins / metabolism
  • Glycoproteins / pharmacology*
  • Mitogens / pharmacology
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Neuregulins
  • Neurons / metabolism
  • Oligodendroglia / cytology*
  • Prosencephalon / cytology
  • Rats
  • Receptor, ErbB-2
  • Receptors, Nerve Growth Factor / genetics
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects*
  • Solubility
  • Stem Cells / cytology


  • Glycoproteins
  • Mitogens
  • Nerve Growth Factors
  • Neuregulins
  • Receptors, Nerve Growth Factor
  • Recombinant Proteins
  • Receptor, ErbB-2