Part F. The Glial Cell–Derived Neurotrophic Factor Signaling Pathway 35 Signaling Pathways of Glial Cell–Derived Neurotrophic Factor

Glial cell–derived neurotrophic factor (GDNF), a distant relativeof transforming growth factor- (TGF-), was purified as a fac-tor that promotes the survival and differentiation of embryonic mes-encephalic dopaminergic neurons (Lin et al., 1993). A closely related protein, neurturin, was purified as a factor that promotes the survival of sympathetic neurons (Kotzbauer et al., 1996). Subsequently, two additional members of the GDNF family of ligands—artemin and persephin—were identified in EST databases (Baloh et al., 1998; Mil-brandt et al., 1998; Masure et al., 1999). Each of these proteins has been shown to function as a survival and differentiation factor for sub-populations of cultured neurons (reviewed in Airaksinen et al., 1999