The role of NFIX in regulating neural stem cell development in postnatal mouse brain
Nuclear Factor I (NFI) family members have been shown to function as transcription factors and regulate the development of multiple organs. Knocking out the Nfix gene resulted in multiple defects during postnatal mouse brain development. Here I show that NFIX is expressed in most neural stem cells (NSCs) and neural progenitor cells (NPCs) in both the subventricular zone and dentate gyrus, which are the two main niches for NSCs during postnatal and adult development. This suggests that NFIX may regulate the development of these cells in a cell-autonomous way. In addition, no NFIX staining is observed in cells in oligodendrocyte (OL)-lineage, indicating that NFIX expression is lost during oligodendrogenesis (ODG) from NSCs. Further in vivo and in vitro studies show that loss of NFIX in NSC increases ODG, while overexpression of NFIX blocks ODG of NSCs. Moreover, genes differentially expressed in OL progenitor cells (OPCs) are enriched in the Nfix -/- NSC culture compared to WT controls. These data indicate that NFIX may regulate a complex network of transcription factors and signaling molecules and thus suppresses ODG of NSCs. In addition to ODG, my collaborative work with other labs shows that NFIX also promotes NSC quiescence and may regulate neuroblast migration. Some preliminary data show that loss of NFIX leads to abnormal NSC neurogenesis and apoptosis. Together, these results indicate that the NFIX transcription factor plays an important role in regulating the development of NSCs in the postnatal mouse brain.