DEVELOPMENT OF MESENCEPHALIC DOPAMINERGIC-NEURONS AND THE TRANSFORMING GROWTH-FACTOR-BETA SUPERFAMILY

Transforming growth factors beta (TGF-beta s) represent a family of mu ltifunctional cytokines affecting growth and differentiation of a larg e variety of cell types. Several members of this family, as e.g. TGF-b eta 2 and -beta 3 as well as glial cell line-derived neurotrophic fact or (GDNF), have recently been shown to be expressed in the developing and adult brain. Their neural functions are therefore in the focus of current research. The present review summarizes the evidence concernin g their expression in the mammalian midbrain and their functions on de veloping dopaminergic neurons. Such functions include promotion of sur vival and protection against N-methyl-4-phenylpyridinium ion (MPP(+)) toxicity. In contrast to many other cytokines affecting these neurons the mechanism of action of the TGF-beta s does not involve cell prolif eration or delivery of growth factors from astroglial cells.