A role for fibroblast growth factor in oligodendrocyte development.
The differentiation of oligodendrocyte-type 2 astrocyte (O-2A) glial progenitor cells into myelin-forming oligodendrocytes is influenced by several polypeptide growth factors. Exposure of O-2A progenitors to basic fibroblast growth factor (bFGF) promotes their sustained proliferation, blocks their differentiation, and maintains both a high level of platelet-derived growth factor (PDGF) alpha-receptors and PDGF sensitivity. Exposure to PDGF, in contrast, promotes only a limited number of cell divisions prior to their differentiation and triggers progenitor cell migration. In the continued presence of bFGF the cells have a stellate morphology with short processes. Upon addition of PDGF these stellate cells become bipolar with long processes, and on removal of PDGF their morphology reverts back to stellate. Thus the phenotype of O-2A progenitor cells in response to these growth factors is plastic. Our studies suggest that bFGF (or a related ligand) in the CNS may sensitize O-2A progenitors to PDGF and thereby initiate their ability to migrate into white matter tracts prior to the onset of myelination.
McKinnon
R D
RD
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Matsui
T
T
Aranda
M
M
Dubois-Dalcq
M
M
D000591:Amino Acid Isomerases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000502:physiology*; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology*; D019696:Peptidylprolyl Isomerase; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor
D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase