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This Article Full Text Full Text (PDF) All Versions of this Article: 575/2/403    most recent jphysiol.2006.113464v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prakash, N. Articles by Wurst, W. Search for Related Content PubMed PubMed Citation Articles by Prakash, N. Articles by Wurst, W. Related Collections Review articles

¹ GSF-National Research Center for Environment and Health, Technical University Munich, Institute of Developmental Genetics, Ingolstaedter Landstr. 1, D-85764 Munich/Neuherberg, Germany
² Max-Planck-Institute of Psychiatry, Kraepelinstr. 2, D-80804 Munich, Germany

Recent data have substantially advanced our understanding of midbrain dopaminergic neuron development. Firstly, a Wnt1-regulated genetic network, including Otx2 and Nkx2-2, and a Shh-controlled genetic cascade, including Lmx1a, Msx1 and Nkx6-1, have been unravelled, acting in parallel or sequentially to establish a territory competent for midbrain dopaminergic precursor production at relatively early stages of neural development. Secondly, the same factors (Wnt1 and Lmx1a/Msx1) appear to regulate midbrain dopaminergic and/or neuronal fate specification in the postmitotic progeny of these precursors by controlling the expression of midbrain dopaminergic-specific and/or general proneural factors at later stages of neural development. For the first time, early inductive events have thus been linked to later differentiation processes in midbrain dopaminergic neuron development. Given the pivotal importance of this neuronal population for normal function of the human brain and its involvement in severe neurological and psychiatric disorders such as Parkinson's Disease, these advances open new prospects for potential stem cell-based therapies. We will summarize these new findings in the overall context of midbrain dopaminergic neuron development in this review.

(Received 15 May 2006; accepted after revision 3 July 2006; first published online 6 July 2006)
Corresponding author W. Wurst: GSF-National Research Center for Environment and Health, Technical University Munich, Institute of Developmental Genetics, Ingolstaedter Landstr. 1, D-85764 Munich/Neuherberg, Germany. Email: wurst{at}gsf.de

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