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A Wnt signal regulates stem cell fate and differentiation in vivo.
Vortrag: International Spring School 2006, 24th July 2006, Rostock, Germany. (2006)
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Our knowledge about the generation of midbrain dopaminergic neurons in vivo is still rudimentary, despite many attempts to recapitulate the underlying events in vitro. Because the loss of these neurons is implicated in Parkinson’s Disease, the lack of information about their development is one of the major drawbacks in the design 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 (Shh), 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 Shh-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 Other: Lecture
Conference Title International Spring School 2006
Conference Date 24th July 2006
Conference Location Rostock, Germany
Institute(s) Institute of Developmental Genetics (IDG)