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

Nature Neuroscience volume 1, pages 374–377 (1998)Cite this article

Abstract

Transforming growth factor (TGF)-α is neurotrophic for midbrain dopaminergic neurons in vitro. Here I investigated whether a null mutation in the TGF-α 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-α 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-α is unlikely to regulate developmental neuron death. These studies indicate that TGF-α is required for the normal proliferation or differentiation of a select population of dopaminergic neurons within the SN.

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Figure 1: TH-immunoreactive cell counts.
Figure 2: TH immunocytochemistry of the striatum.
Figure 3: TH-immunoreactive cell counts in the SN of postnatal day 1 TGF-α+/+ and TGF-α–/– mice.

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Acknowledgements

I would like to thank John Morrison and members of his laboratory for support and discussions concerning the stereological methods used in this study, Peter Rapp for comments on the manuscript, and Susan Lasky and Jeremy Kay for technical support. This work was supported by NIH grant AG08538.

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  1. Fishberg Research Center for Neurobiology, Mt. Sinai School of Medicine, One Gustave Levy Place, Box 1065, New York, 10029, New York, USA

    Mariann Blum

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Correspondence to Mariann Blum.

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Blum, M. A null mutation in TGF-α leads to a reduction in midbrain dopaminergic neurons in the substantia nigra. Nat Neurosci 1, 374–377 (1998). https://doi.org/10.1038/1584

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