Glial cell mitogens bFGF and PDGF differentially regulate development of O4+GalC- oligodendrocyte progenitors.
The oligodendrocyte lineage in cerebrum is characterized by the expression of immunologically identified surface antigens resulting in the sequential appearance of three distinct phenotypes, A2B5+O4-, O4+GalC-, and O4+GalC+. In the present study we have placed O4+GalC- progenitors immunopanned from premyelinating rat cerebrum into a basal, defined medium that by itself does not support well either their proliferation or survival. The response of these progenitor cells to platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) was then examined. The results demonstrate that both PDGF and bFGF stimulated proliferation and short-term survival of newly cultured cells, but that their effect on the course of O4+GalC- differentiation was strikingly different. PDGF delayed postmitotic development by transiently reverting (ED50 = 3 ng/ml) O4+GalC- progenitors to A2B5+O4- preprogenitor-like cells that subsequently differentiated even in the continued presence of PDGF. bFGF restored mitogenic activity of the O4+GalC- progenitors to a saturable level at low doses (ED50 = 1 ng/ml); doses of bFGF > or = 10 ng/ml impaired differentiation of the progenitors into GalC+ cells and were also mitogenic for newly differentiated GalC+ oligodendrocytes. These data imply that bFGF supplants PDGF as a mitogen during lineage progression from A2B5+O4- to O4+GalC- progenitors. Lineage reversion of O4+GalC- cells in response to PDGF is suggested as a mechanism for facilitating remyelination by triggering the proliferative expansion of O4+GalC- progenitor-like cells persisting into adulthood.
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Department of Microbiology, University of Connecticut Medical School, Farmington 06030.
Pfeiffer
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D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2