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

Cell and Tissue Research volume 318, pages 23–33 (2004)Cite this article

Abstract

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.

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Acknowledgements

The authors thank M. Wiehle for his support in preparing the manuscript.

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  1. Department for Neuroanatomy, Center of Anatomy, Georg-August-University Göttingen, 37075, Göttingen, Germany

    Eleni Roussa & Kerstin Krieglstein

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  1. Eleni Roussa
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Correspondence to Eleni Roussa.

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The work carried out in the authors’ laboratories was supported by grants from the Deutsche Forschungsgemeinschaft

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Roussa, E., Krieglstein, K. Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8, and TGF-β. Cell Tissue Res 318, 23–33 (2004). https://doi.org/10.1007/s00441-004-0916-4

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  • DOI: https://doi.org/10.1007/s00441-004-0916-4

Keywords

  • Phenotype induction
  • TGF-β
  • SHH
  • FGF8
  • Dopaminergic neurons