A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra.

Transforming growth factor (TGF)-alpha is neurotrophic for midbrain dopaminergic neurons in vitro. Here I investigated whether a null mutation in the TGF-alpha gene affects the normal development or survival of dopaminergic neurons in either the substantial nigra (SN) or the ventral tegmental area (VTA). The SN of TGF-alpha knockout mice contained 50% fewer dopaminergic neurons than the control SN, but VTA neuron number was unchanged. In addition, the overall volume of the dorsal striatum was reduced by 20%. Newborn mice showed a similar decrease in the number of SN dopaminergic neurons, suggesting that TGF-alpha is unlikely to regulate developmental neuron death. These studies indicate that TGF-alpha is required for the normal proliferation or differentiation of a select population of dopaminergic neurons within the SN.