Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoter.

Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, and the noradrenergic neurons of the locus coeruleus. To investigate the regulation of cell type-specific TH expression, we cloned and sequenced a 5.5kb fragment of human genomic DNA immediately 5(') of the TH coding region.

Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenotypes in the Nurr1-overexpressing neural stem cell.

Neural stem cells are self-renewing cells capable of differentiating into all neural lineage cells in vivo and in vitro. In the present study, coordinated induction of midbrain dopaminergic phenotypes in an immortalized multipotent neural stem cell line can be achieved by both overexpression of nuclear receptor Nurr1, and fibroblast growth factor-8 (FGF-8), and sonic hedgehog (Shh) signals. Nurr1 overexpression induces neuronal differentiation and confers competence to respond to extrinsic signals such as Shh and FGF-8 that induce dopaminergic fate in a mouse neural stem cell line.