Midbrain dopaminergic (mdDA) neuron generation crucially depends on the cooperative action of the transcription factors Nurr1 and Pitx3, but little is known about their transcriptional targets. Now, on p. 2363, Marten Smidt and colleagues identify three novel Nurr1 target genes in mice. Through a combination of microarray, chromatin immunoprecipitation and gene expression studies on normal and Nurr1-deficient midbrain tissue, as well as on a Nurr1-overexpressing midbrain-derived cell line, the authors establish that Dlk1, Ptpru and Klhl1 are Nurr1 target genes. They also show that Ptpru and Klhl1 expression in mdDA neurons is Pitx3 dependent, whereas Dlk1 expression does not require Pitx3. Their gene expression analysis of several mdDA markers in Dlk1 knockout mice revealed that Dat, a gene involved in dopamine metabolism, is expressed prematurely in certain dopaminergic precursor cells of these animals. Taken together, these data underscore the complexity of Nurr1-Pitx3 downstream activity and represent an important advance towards understanding the intricate regulatory networks that govern mdDA neuron development.
Dopaminergic gene regulatory network comes into view
Dopaminergic gene regulatory network comes into view. Development 15 July 2009; 136 (14): e1405. doi:
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