Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) Regulates Survival of Midbrain Dopaminergic Neurons

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF-family of ligands signaling via the EGF-receptor tyrosine kinase. In the present study we show that HB-EGF which is expressed in close proximity of developing mesencephalic dopaminergic neurons promotes the survival of TH-positive neurons in vitro. The survival promoting effect of HB-EGF is mediated via astroglial cells and utilizes the MAPK as well as the Akt-signaling pathway. Most notably endogenous HB-EGF significantly contributes to the survival of TH-+ neurons in control cultures, suggesting a relevant developmental role of HB-EGF for dopaminergic neurons. These findings indicate that HB-EGF may be an important molecule for developing dopaminergic neurons of the ventral midbrain.