TRANSFORMING-GROWTH-FACTOR-BETA MEDIATES THE NEUROTROPHIC EFFECT OF FIBROBLAST GROWTH FACTOR-2 ON MIDBRAIN DOPAMINERGIC-NEURONS

Fibroblast growth factor (FGF)-2 is an established neurotrophic factor for dopaminergic (DAergic) neurons in the ventral midbrain. Its survi val and differentiation-promoting effects on DAergic neurons in vitro and in vivo are crucially dependent on the presence, numerical expansi on and maturation of astroglial cells. We show now that transforming g rowth factor (TGF)-beta, an established trophic factor for DAergic neu rons and product of astroglial cells, mediates the trophic effect of F GF-2 on DAergic neurons cultured from the embryonic rat midbrain floor . Antibodies to TGF-beta that neutralize the isoforms -beta 1, -beta 2 and -beta 3 abolish the trophic effect of FGF-2. FGF-2 increases TGF- beta 3 mRNA and amounts of biologically active TGF-beta determined in a mink lung epithelial cell assay in a time-dependent manner. FGF-2 al so induces levels of active TGF-beta in neonatal rat astrocytes cultur ed from midbrain, striatum and cortex. We conclude that TGF-beta is re quired for mediating the survival promoting effect of FGF-2 on DAergic and, possibly, cortical and striatal neurons grown in the presence of glial cells.