The orphan nuclear receptor Nurr1 and the transcription factor Pitx3 are key regulators of dopaminergic (DA) neuron specification in the meso-diencephalic (md) region, which has been intensively studied owing to the importance of mdDA neurons in Parkinson's disease. Now, Marten Smidt and colleagues demonstrate a functional relationship between these two factors(p. 531). The authors show that both Nurr1 and Pitx3 bind to the co-repressor PSF and that both target the same genomic promoter regions, suggesting that Pitx3 might regulate the activity of the Nurr1 transcriptional complex. Indeed, in Pitx3-/- embryos, Nurr1 target gene expression is reduced,in accordance with increased interaction between Nurr1 and the co-repressor SMRT. The researchers also succeeded in partially rescuing Nurr1 target gene expression by interfering with SMRT signalling activity. Based on these findings, the authors propose a novel model in which Pitx3 regulates the capacity of Nurr1 to induce mdDA neuron specification by inducing the release of the SMRT repressor from the Nurr1 transcriptional complex.
IN THIS ISSUE|
15 February 2009
Pitx3 SM(a)RTly derepresses DA neurons
Online ISSN: 1477-9129
Print ISSN: 0950-1991
© 2009.
2009
Development (2009) 136 (4): e401.
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Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression
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Pitx3 SM(a)RTly derepresses DA neurons. Development 15 February 2009; 136 (4): e401. doi:
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