GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors.
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.
Canoll
P D
PD
Department of Pharmacology, New York University Medical School, New York 10016, USA.
Musacchio
J M
JM
Hardy
R
R
Reynolds
R
R
Marchionni
M A
MA
Salzer
J L
JL
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D020880:Neuregulins; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D016548:Prosencephalon / Q000166:cytology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D012995:Solubility; D013234:Stem Cells / Q000166:cytology
D006023:Glycoproteins; D008934:Mitogens; D009414:Nerve Growth Factors; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins