Regulatory interactions between Vax1, Pax6, and miR-7 regionalize the lateral Ventricular-Subventricular Zone during post-natal Olfactory Bulb neurogenesis in mice

Abstract

Several subtypes of interneurons destined for the olfactory bulb are continuously generated after birth by neural stem cells located in the ventricular-subventricular zones of the lateral ventricles. Future neuronal identity depends on the positioning of pre-determined neural stem cells along the ventricle walls, which, in turn, depends on delimited expression domains of transcription factors and their cross regulatory interactions. However, mechanisms underlying positional identity of neural stem cells are still poorly understood. Here we show that the transcription factor Vax1 controls the production of two specific neuronal sub-types. First, it is directly necessary to generate Calbindin expressing interneurons from ventro-lateral progenitors. Second, it represses the generation of dopaminergic neurons by dorso-lateral progenitors through inhibiting Pax6 expression in the dorso-lateral wall. We provide evidence that this repression occurs via activation of microRNA miR-7, targeting Pax6 mRNA.