INDUCTION OF DOPAMINERGIC NEURON PHENOTYPE IN THE MIDBRAIN BY SONIC HEDGEHOG PROTEIN

Loss of substantia nigra dopaminergic neurons, which develop from the ventral region of the midbrain, is associated with Parkinson's disease . During embryogenesis, induction of these and other ventral neurons i s influenced by interactions with the underlying mesoderm of the notoc hord and the floor plate, which lies at the ventral midline of the dev eloping CNS. Sonic hedgehog encodes a secreted peptide, which is expre ssed in notochord and floor plate cells and can induce appropriate ven tral cell types in the basal forebrain and spinal cord. Here we demons trate that Sonic hedgehog is sufficient to induce dopaminergic and oth er neuronal phenotypes in chick mesencephalic explants in vitro. We fi nd that Sonic hedgehog is a general ventralizing signal in the CNS, th e specific response being determined by the receiving cells. These res ults suggest that Sonic hedgehog may have utility in the induction of clinically important cell types.