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First published online January 23, 2009

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Pitx3 SM(a)RTly derepresses DA neurons

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.

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Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression

Frank M. J. Jacobs, Susan van Erp, Annemarie J. A. van der Linden, Lars von Oerthel, J. Peter H. Burbach, and Marten P. Smidt
Development 2009 136: 531-540. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?