miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons.

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Bibliographic Details
Title:	miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons.
Authors:	de Chevigny, Antoine, Coré, Nathalie, Follert, Philipp, Gaudin, Marion, Barbry, Pascal, Béclin, Christophe, Cremer, Harold
Source:	Nature Neuroscience. Aug2012, Vol. 15 Issue 8, p1120-1126. 7p. 6 Graphs.
Subjects:	Dopaminergic neurons, Cellular control mechanisms, Genetic regulation, Neural stem cells, Prosencephalon, Gene expression, Laboratory mice
Abstract:	In the postnatal and adult mouse forebrain, a mosaic of spatially separated neural stem cells along the lateral wall of the ventricles generates defined types of olfactory bulb neurons. To understand the mechanisms underlying the regionalization of the stem cell pool, we focused on the transcription factor Pax6, a determinant of the dopaminergic phenotype in this system. We found that, although Pax6 mRNA was transcribed widely along the ventricular walls, Pax6 protein was restricted to the dorsal aspect. This dorsal restriction was a result of inhibition of protein expression by miR-7a, a microRNA (miRNA) that was expressed in a gradient opposing Pax6. In vivo inhibition of miR-7a in Pax6-negative regions of the lateral wall induced Pax6 protein expression and increased dopaminergic neurons in the olfactory bulb. These findings establish miRNA-mediated fine-tuning of protein expression as a mechanism for controlling neuronal stem cell diversity and, consequently, neuronal phenotype. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	In the postnatal and adult mouse forebrain, a mosaic of spatially separated neural stem cells along the lateral wall of the ventricles generates defined types of olfactory bulb neurons. To understand the mechanisms underlying the regionalization of the stem cell pool, we focused on the transcription factor Pax6, a determinant of the dopaminergic phenotype in this system. We found that, although Pax6 mRNA was transcribed widely along the ventricular walls, Pax6 protein was restricted to the dorsal aspect. This dorsal restriction was a result of inhibition of protein expression by miR-7a, a microRNA (miRNA) that was expressed in a gradient opposing Pax6. In vivo inhibition of miR-7a in Pax6-negative regions of the lateral wall induced Pax6 protein expression and increased dopaminergic neurons in the olfactory bulb. These findings establish miRNA-mediated fine-tuning of protein expression as a mechanism for controlling neuronal stem cell diversity and, consequently, neuronal phenotype. [ABSTRACT FROM AUTHOR]
ISSN:	10976256
DOI:	10.1038/nn.3142