Developmental expression of fibroblast growth factor (FGF) receptors in neural stem cell progeny. Modulation of neuronal and glial lineages by basic FGF treatment

Neural stem cells (NSCs) are self-renewable, multipotential cells capable o f differentiating into the three major neural cell types, but the mechanism s which regulate their development are not fully understood, Both basic fib roblast growth factor (bFGF) and epidermal growth factor (EGF) promote the proliferation of NSCs. However, studies on the role of FGFs in the differen tiation of EGF-expanded NSCs are still incomplete. We have studied the expr ession of distinct FGF receptors (FGFRs) in the progeny of EGF-expanded NSC s isolated from E15 rat striatum. In situ hybridization analysis and immuno cytochemistry showed a developmentally related expression pattern and a cel l lineage-specific distribution of these receptors. FGFR1 and FGFR2 were id entified in many early precursors and in the oligodendrocyte lineage. The l atter receptor was also present in a subpopulation of astrocytes. FGFR3 was detected in a restricted population of early precursors, in oligodendrogli al progenitors, and in neurons and protoplasmic astrocytes of late-term cul tures. Basic FGF treatment of the progeny of NSCs increased the proliferati ve rate of precursors and the number of oligodendrocytes generated, whereas the number of differentiating neurons was significantly reduced. Together these data provide evidence that FGFs modulate the development of EGF-expan ded NSCs, and that this is at least partly determined by a cell lineage-spe cific expression of multiple FGFRs.