Distinct effects of bFGF and PDGF on oligodendrocyte progenitor cells.
We have compared the effects of platelet-derived (PDGF) and basic fibroblast (bFGF) growth factors on the shape, migration, and differentiation of oligodendrocyte progenitor cells, the precursors of myelin-forming cells in the CNS. In the presence of bFGF, oligodendrocyte progenitors purified from rat neonatal brain cultures were stellate, non-motile, and had a morphological complexity of 1.26 +/- 0.03 as measured by fractal dimension (D). These cells expressed transcripts encoding the POU-homeodomain transcription factor Oct-6, but not myelin genes. Upon addition of PDGF, bFGF-treated cells became motile and twofold less complex in shape (D = 1.19 +/- 0.03). These changes occurred within 6 +/- 4 h and were dependent on de novo transcription and translation, but not DNA synthesis. Upon removal of PDGF the cells reverted to their stellate shape (D = 1.26). Removal of both bFGF and PDGF resulted in oligodendrocyte differentiation after 3 days, with a fourfold increase in complexity of shape (D = 1.55 +/- 0.08), loss of Oct-6 transcripts, and gain of myelin transcripts. Thus PDGF is both necessary and sufficient to induce a motile state in progenitor cells growing in the presence of bFGF. Together with our previous data (McKinnon et al.: Neuron 5:603, 1990), our results suggest that bFGF and PDGF may control distinct phases of proliferation and migration of oligodendrocyte progenitor cells in vivo.
McKinnon
R D
RD
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Smith
C
C
Behar
T
T
Smith
T
T
Dubois-Dalcq
M
M
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2