Fibroblast growth factor-9 modulates the expression of myelin related proteins and multiple fibroblast growth factor receptors in developing oligodendrocytes.
The effect of fibroblast growth factor (FGF)-9 on the expression of FGF receptors (FGFR) and the major myelin proteins was examined in cultures of developing rat brain oligodendrocytes (OLs), using immunological techniques. FGFR-1, -3, and -4 were expressed at all developmental stages but were not present in isolated myelin fractions. By contrast, FGFR-2 protein was predominantly localized to differentiating cells and myelin. FGF-9 altered FGFR and myelin protein levels during OL differentiation; there was increased expression of FGFR-1 and decreased levels of both FGFR-2 and myelin proteins. Further, FGF-9 stimulated mitogen-associated protein kinase (MAPK) phosphorylation. The effect of FGF-9 on MAPK, however, was transient and less robust in progenitor cells than in differentiated oligodendrocytes. The effects of FGF-9 and FGF-2 on FGFR and myelin protein levels were comparable; both up-regulated FGFR-1, and down-regulated FGFR-2, CNP, PLP and MBP. These findings suggest that FGF-9 may be important for glial cell development.
Cohen
R I
RI
National Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-4160, USA. cohenr@ninds.nih.gov
Chandross
K J
KJ
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D017628:Microglia / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
C496461:Fgf9 protein, rat; D051525:Fibroblast Growth Factor 9; D006133:Growth Substances; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020928:Mitogen-Activated Protein Kinases; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat