The inhibition of oligodendrocytic differentiation of O-2A progenitors caused by basic fibroblast growth factor is overridden by astrocytes.
The inhibition of differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitors into oligodendrocytes caused by basic fibroblast growth factor (bFGF) can be overcome by non-O-2A lineage cells present in the optic nerve and by astrocytes purified from cerebral cortices. Although purified O-2A progenitors grown in the presence of bFGF for up to 6 days were inhibited from differentiating into oligodendrocytes, O-2A progenitors growing in heterogeneous optic nerve cultures did not show a similar inhibition of differentiation. The factor(s) responsible for overriding the inhibitory effects of bFGF appeared to be secreted by astrocytes, as extensive generation of oligodendrocytes was seen in cultures of purified O-2A progenitors exposed to bFGF+ medium conditioned by purified astrocytes (ACM). In addition, purified O-2A progenitors displayed a remarkable sensitivity to bFGF, which extended at least down to concentrations of 0.03 ng/ml, a concentration of < 2 x 10(-12) M. At a bFGF concentration of just 0.1 ng/ml, this mitogen still promoted DNA synthesis in as many O-2A progenitors as in cultures exposed to 1-30 ng/ml of this growth factor, but exhibited a reduced ability to promote DNA synthesis in oligodendrocytes. In addition, although concentrations of bFGF as low as 0.03 ng/ml were a potent stimulator of DNA synthesis in O-2A progenitors, application of this amount of bFGF no longer inhibited the differentiation of progenitors into oligodendrocytes as effectively as application of higher bFGF concentrations. Thus, the induction of DNA synthesis by bFGF can be uncoupled from the inhibition of differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ludwig Institute for Cancer Research, London, UK.
M
M
Mayer
O
O
Bögler
M
M
Noble
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007700:Kinetics; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D009900:Optic Nerve / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2