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.
Blum
M
M
Fishberg Research Center for Neurobiology, Mt. Sinai School of Medicine, New York, New York 10029, USA. blum@cortex.neuro.mssm.edu
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D013378:Substantia Nigra / Q000166:cytology* / Q000201:enzymology; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016211:Transforming Growth Factor alpha; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine