Reciprocal transcriptional repression between pax6 and olig2 regulates neuronal vs. glial fate in the neonatal subventricular zone

The neonatal forebrain subventricular zone (SVZ), which generates both interneurons and glia, contains a heterogeneous mixture of progenitors. It is not known how cell fate decisions are derived in this population. Here, we investigated if two transcription factors, Pax6 and Olig2, play roles in specifying cell fates. We found that Pax6 and Olig2 have mutually exclusive expression patterns and provided evidence that each factor represses the transcription of the gene encoding the other factor by using in sliico and in vitro techniques. Finally, we used in vivo retro- or lenti-virus injections into SVZ to demonstrate that pax6 expression promotes neurogenesis, while olig2 expression promotes gliogenesis. The reciprocal transcriptional repression of these genes provides one mechanism underlying neuronal vs. glial fate decisions and suggests a feedback system in which small changes in the expression of one factor can be amplified into larger changes, thus reinforcing a particular fate choice.