A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo

Nilima Prakash, Claude Brodski, Thorsten Naserke, Eduardo Puelles, Robindra Gogoi, Anita Hall, Markus Panhuysen, Diego Echevarria, Lori Sussel, Daniela M. Vogt Weisenhorn, Salvador Martinez, Ernest Arenas, Antonio Simeone, Wolfgang Wurst

    Research output: Contribution to journalArticlepeer-review

    216 Scopus citations

    Abstract

    Midbrain neurons synthesizing the neurotransmitter clopamine play a central role in the modulation of different brain functions and are associated with major neurological and psychiatric disorders. Despite the importance of these cells, the molecular mechanisms controlling their development are still poorly understood. The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons. Here, we show that Wnt1 regulates the genetic network, including Otx2 and Nkx2-2, that is required for the establishment of the midbrain dopaminergic progenitor domain during embryonic development. In addition, Wnt1 is required for the terminal differentiation of midbrain dopaminergic neurons at later stages of embryogenesis. These results identify Wnt1 as a key molecule in the development of midbrain dopaminergic neurons in vivo. They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease.

    Original languageEnglish
    Pages (from-to)89-98
    Number of pages10
    JournalDevelopment (Cambridge)
    Volume133
    Issue number1
    DOIs
    StatePublished - 1 Jan 2006

    Keywords

    • Cell fate specification
    • Development
    • Dopaminergic neuron
    • Midbrain
    • Mouse
    • Nkx2-2
    • Otx2
    • Progenitor domain
    • Wnt1

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology

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