The inhibition of oligodendrocytic differentiation of O‐2A progenitors caused by basic fibroblast growth factor is overridden by astrocytes

Abstract

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)

A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development.

“…ARIA induces tyrosine phosphorylation of one or more -185-kDa proteins thought to be homologous to members of the Neu/ErbB/HER family ofreceptor tyrosine kinases (8)(9)(10)(11). We expanded the number of 02A progenitors in culture with PDGF-AA and bFGF (27) and from these derived three populations of cells to assay the effects of ARIA on protein tyrosine phosphorylation: (i) 02A progenitors maintained in a proliferating state by continuous exposure to PDGF-AA and bFGF, (ii) oligodendrocytes maintained in DM01j for 4 days, and (iii) type II astrocytes maintained in 5% fetal bovine serum for 4 days. The cultures were then treated with control solution or ARIA for 1 and 5 min.…”

Fibroblast Growth Factors and Their Receptors in Oligodendrocyte Development: Implications for Demyelination and Remyelination

“…It has been proposed that FGF-2 establishes the sensitivity of OL progenitors to PDGF [McKinnon et al, 1990]. FGF-2 by itself stimulates proliferation of purified Late progenitors and blocks their terminal differentiation in culture at high doses; upon removal of FGF-2, cells readily enter terminal differentiation [McKinnon et al, 1990;Gard and Pfeiffer 1993;Bansal and Pfeiffer, 1994]; however this inhibition can be overridden in the presence of astrocytes [Bögler et al, 1990;Mayer et al, 1993]. Thus the role of FGF-2 in OL proliferation may be to 'finetune' the timing of terminal differentiation, perhaps by an interplay of its own receptor expression pattern as well as regulating the 'cross-talk' with other growth factor systems (see below).…”

PKC-η mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways

“…Upstream of PKCs, platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, and cilliary neurotrophic factor help drive glial progression towards astrocytic and oligonedrocytic differentiation (Bogler et al, 1990;McKinnon et al, 1990;Mayer et al, 1993Mayer et al, , 1994Rajan and Mckay, 1998). Expression levels of genes encoding growth factors and growth factor receptors that control glial cell differentiation are frequently elevated in gliomas (Ekstrand et al, 1991;Guha et al, 1995;Weis et al, 1999).…”