Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve.
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.
Fernandez
P A
PA
Department of Biology, University College London, United Kingdom.
Tang
D G
DG
Cheng
L
L
Prochiantz
A
A
Mudge
A W
AW
Raff
M C
MC
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy; D019556:COS Cells; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D014162:Transfection
D020890:Neuregulin-1