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Open Access Green as soon as Postprint is submitted to ZB.
A Wnt signal regulates stem cell fate and differentiation in vivo.
Neurodegener. Dis. 4, 333-338 (2007)
Our knowledge about the normal generation of midbrain dopaminergic neurons in vivois still rudimentary, despite many attempts to recapitulate the underlying events in vitro. Because the loss of these neurons is implicated in Parkinson's disease, this lack of information is one of the major drawbacks in the development of better therapies for this severe human neurological disorder. Recently, substantial advances have been made by demonstrating that the secreted molecule Wnt1 regulates a genetic network, including the transcription factors Otx2 and Nkx2-2, for the initial establishment of the dopaminergic progenitor domain in the mammalian ventral midbrain. In addition, Wnt1 appears to regulate the differentiation of the postmitotic progeny of these precursors by initiating the expression of midbrain dopaminergic-specific transcription factors. A genetic cascade controlled by the secreted molecule Sonic hedgehog, including the transcription factors Lmx1a, Msx1 and Nkx6-1, acts in parallel with the Wnt1-regulated network to establish the midbrain dopaminergic progenitor domain. The Sonic-hedgehog-controlled cascade may diverge from the Wnt1-regulated network at later stages of neural development through induction of proneural transcription factors required for the acquisition of generic neuronal properties by the midbrain dopaminergic progeny. Here we provide a brief overview of these regulatory gene networks.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Parkinson's disease; Dopamine neuron; Ventral midbrain
ISSN (print) / ISBN
1660-2854
e-ISSN
1660-2862
Journal
Neurodegenerative Diseases
Quellenangaben
Volume: 4,
Issue: 4,
Pages: 333-338
Publisher
Karger
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)