miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons.
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.
Institut de Biologie de Développement de Marseille-Luminy, Aix-Marseille University, Marseille, France.
Antoine
A
de Chevigny
Nathalie
N
Coré
Philipp
P
Follert
Marion
M
Gaudin
Pascal
P
Barbry
Christophe
C
Béclin
Harold
H
Cremer
D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism* / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D016548:Prosencephalon / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology
D005136:Eye Proteins; D018398:Homeodomain Proteins; C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins