Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters

Basic fibroblast growth factor (bFGF) has been shown to influence thesurvival, proliferation and differentiation of a variety of cell types inthe nervous system. In this investigation we have examined the action ofbFGF on: (i) the rate of proliferation; (ii) cell cycle parameters; (iii)the maintenance of cell division; (iv) the recruitment of quiescent cells;and (v) the degree of differentiation of cortical progenitor cells incultures prepared from E16 rat embryos. The proliferation rate (labellingindex) of cortical progenitor cells doubled in the presence of bFGF over 48h. However, the lengths of the cell cycle phases were unchanged. Clonesmarked with a recombinant retrovirus on the first day in vitro (DIV) grewsignificantly larger in the presence of bFGF. Furthermore, many of theclones examined in control cultures had ceased to divide after a maximum offour cell cycles, whereas almost all clonally related cells were stilldividing in the presence of bFGF 4 days later, i.e. for at least six cellcycles. Basic FGF also stimulated the division of quiescent progenitorcells, which otherwise would have differentiated or undergone cell death.The degree of neuronal and glial differentiation was studied after 5 DIVusing MAP-2 and GFAP immunocytochemistry. In the presence of bFGF, thepercentage of MAP-2-labelled cells was less than half that of controlcultures, whereas the number of cells immunoreactive for nestin (a markerof progenitor cells) remained very high. Cells immunoreactive for GFAP werepresent in bFGF-treated cultures, yet were extremely rare in controlconditions. These experiments show that bFGF, a potent mitogen for corticalprogenitor cells, has no effects on the parameters of their cell cycle butextends their proliferative capability, promotes their survival and delaystheir differentiation into neurons.