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Background  The forebrain subventricular zone (SVZ) of neonatal mammals contains a large, heterogeneous population of migratory and proliferating precursors of interneurons and glia. These cell types are produced in large numbers in the immediate postnatal period, the glioblasts populating the hemispheres with astrocytes and oligodendrocytes, the neuroblasts migrating to the olfactory bulb to become interneurons. How cell fate decisions are determined or stabilized in this mixed population is not clear, although previous studies indicate the importance of two transcription factors, Pax6 in neurons and Olig2 in glia, and suggest there may be reciprocal repression between these genes.    Methodology/Principal Findings  In examining the SVZ of neonatal mouse and rat brain, we find that the very large majority of SVZ cells express either Pax6 or Olig2, but few express both. We have used  in vivo  retro- and lenti-virus injections into the neonatal SVZ and  in vitro  gene transfer to demonstrate that  pax6  over-expression is sufficient to down-regulate  olig2  and to promote a neuronal lineage development and migration pattern in  olig2 -expressing cells. Furthermore, we provide evidence that Pax6 binds to the  olig2  promoter and that an HEB sequence in the promoter is required for the Pax6 repression of  olig2  transcription. Lastly, we constructed a lentivirus to target  olig2 -expressing cells in the SVZ to trace their fates, and found that the very large majority developed into glia.    Conclusions/Significance  We provide evidence for a direct repression of  olig2  by Pax6. Since SVZ cells can display developmental plasticity  in vitro , the cross-repression promotes a stabilization of cell fates. This repression may be critical in a germinal zone in which immature cells are highly migratory and are not organized into an epithelium.

Pax6 Expression Is Sufficient to Induce a Neurogenic Fate in Glial Progenitors of the Neonatal Subventricular Zone