Development of mesencephalic dopaminergic neurons and the transforming growth factor-beta superfamily.

Transforming growth factors beta (TGF-beta s) represent a family of multifunctional cytokines affecting growth and differentiation of a large variety of cell types. Several members of this family, as e.g. TGF-beta 2 and -beta 3 as well as glial cell line-derived neurotrophic factor (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 concerning their expression in the mammalian midbrain and their functions on developing dopaminergic neurons. Such functions include promotion of survival 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 proliferation or delivery of growth factors from astroglial cells.