Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8, and TGF-beta

Cell-fate decisions along the dorsoventral and anterior-posterior axis of the neural tube are dictated by factors from signaling and organizing centers. According to the prevailing notion, the formation of mesencephalic dopaminergic neurons is directed by diffusable signals from the notochord, floor...

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Bibliographic Details
Published in:Cell and tissue research 2004-10, Vol.318 (1), p.23-33
Main Authors: Roussa, Eleni, Krieglstein, Kerstin
Format: Article
Language:English
Subjects:
Animals
Dopamine - physiology
Fibroblast Growth Factor 8
Fibroblast Growth Factors - physiology
Gene Expression Regulation, Developmental - physiology
Hedgehog Proteins
Humans
Mesencephalon - cytology
Mesencephalon - embryology
Mesencephalon - physiology
Neurons - physiology
Trans-Activators - physiology
Transforming Growth Factor beta - physiology
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Summary:Cell-fate decisions along the dorsoventral and anterior-posterior axis of the neural tube are dictated by factors from signaling and organizing centers. According to the prevailing notion, the formation of mesencephalic dopaminergic neurons is directed by diffusable signals from the notochord, floor plate, and isthmic organizer. Sonic hedgehog (Shh), secreted by the notochord and floor plate, and fibroblast growth factor (FGF) 8, secreted by the isthmus, are thought to be key molecules involved in the development of midbrain dopaminergic neurons. During the last decade, the introduction of elegant explant culture systems and the generation of transgenic and mutant mice have greatly contributed to a better understanding of the molecular signals that direct the induction and specification of midbrain dopaminergic neurons. In this context, experimental evidence has challenged the dominant roles of Shh and FGF8 in dopaminergic neuron development. Additional molecules have been identified as being required for the generation of mesencephalic dopaminergic neurons, particularly members of the transforming growth factor beta superfamily.
ISSN:0302-766X
DOI:10.1007/s00441-004-0916-4