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Development of mesencephalic dopaminergic neurons and the transforming growth factor-beta superfamily
K Krieglstein1, C Suter-Crazzolara, K Unsicker
1Department of Anatomy and Cell Biology, University of Heidelberg, Federal Republic of Germany.
Abstract:
Transforming growth factors beta (TGF-beta s) represent a family of multifunctional cytokines affecting growth and differentiation of a large variety of cell types. Several members of this family, as e.g. TGF-beta 2 and -beta 3 as well as glial cell line-derived neurotrophic factor (GDNF), have recently been shown to be expressed in the developing and adult brain. Their neural functions are therefore in the focus of current research. The present review summarizes the evidence concerning their expression in the mammalian midbrain and their functions on developing dopaminergic neurons. Such functions include promotion of survival and protection against N-methyl-4-phenylpyridinium ion (MPP+) toxicity. In contrast to many other cytokines affecting these neurons the mechanism of action of the TGF-beta s does not involve cell proliferation or delivery of growth factors from astroglial cells.
Insights
Transforming growth factors beta (TGF-beta s) promote survival and protect developing dopaminergic neurons in the midbrain from toxicity. Their mechanism differs from other cytokines, not involving cell proliferation or astroglial growth factor delivery.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Transforming growth factors beta (TGF-beta s) are multifunctional cytokines influencing cell growth and differentiation.
- Members like TGF-beta 2, TGF-beta 3, and glial cell line-derived neurotrophic factor (GDNF) are found in the developing and adult brain.
- Neural functions of these factors are a key area of current research.
Purpose of the Study:
- To review the expression of TGF-beta s in the mammalian midbrain.
- To summarize their functions on developing dopaminergic neurons.
Main Methods:
- Literature review of studies on TGF-beta expression and function in the mammalian midbrain.
- Analysis of evidence regarding neurotrophic and neuroprotective roles.
Main Results:
- TGF-beta s are expressed in the mammalian midbrain.
- They promote the survival of developing dopaminergic neurons.
- They offer protection against N-methyl-4-phenylpyridinium ion (MPP+) toxicity.
Conclusions:
- The mechanism of TGF-beta action on dopaminergic neurons does not involve cell proliferation.
- TGF-beta s do not rely on growth factor delivery from astroglial cells for their function.