Fibroblast growth factor-2 inhibits myelin production by oligodendrocytes in vivo.
Fibroblast growth factor-2 (FGF-2) controls in part the timely differentiation of oligodendrocytes into the myelin-producing cells of the CNS. However, although differentiated oligodendrocytes express FGF receptors (R), the effect of FGF-2 on myelin-producing oligodendrocytes in vivo was unknown. In the present study, we show that delivery of FGF-2 into the cerebrospinal fluid of anaesthetized rat pups, aged postnatal day (P) 6 to 9, induced a severe loss of myelin in the caudal anterior medullary velum (AMV). Furthermore, we show that the caudal AMV was myelinated at the time of treatment, so the effects of FGF-2 represent a loss of myelin and not delayed differentiation. This was confirmed by injection of platelet-derived growth factor-AA (PDGF-AA), a factor known to affect the differentiation of PDGF-alphaR expressing oligodendrocyte progenitors, but which did not induce myelin loss in the caudal AMV and did not affect differentiated oligodendrocytes, which do not express PDGF-alphaR. Compared to controls treated with saline or PDGF-AA, FGF-2 induced an accumulation of PLP protein and MBP mRNA within the somata of myelin-producing oligodendrocytes. The results indicate that FGF receptor signalling disrupts myelin production in differentiated oligodendrocytes in vivo and interrupted the transport of myelin-related gene products from the oligodendrocyte cell body to their myelin sheaths.
Goddard
D R
DR
Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, United Kingdom.
Berry
M
M
Kirvell
S L
SL
Butt
A M
AM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009185:Myelin Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology
D006131:Growth Inhibitors; D009185:Myelin Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2