Reduced proliferation and excess astrogenesis of Pax6 heterozygous neural stem/progenitor cells

Neural stem/progenitor cells (NSPCs) are generated in early embryonic brains and maintained to produce neurons and glial cells in the central nervous system throughout the lifespan. A transcription factor Pax6 is a pivotal player in various neurodevelopmental processes. Previously, we have shown that Pax6 heterozygous rodents have defects in hippocampal neurogenesis and production of olfactory bulb interneurons. However, characters of NSPCs derived from Pax6 heterozygous rodents have not been studied in vitro. Here we examined the maintenance/proliferation and differentiation of Pax6 heterozygous mutant (rSey2/+) rat NSPCs in the neurosphere culture system. We found that the proliferative activity of NSPCs derived from rSey2/+ rats was reduced after serial passages. We also observed an excess astrogenesis in serially passaged NSPCs from rSey2/+ rats. These results show that Pax6 is essential for maintaining NSPCs and determining their differentiation fates.

► We evaluated Pax6 heterozygous neural stem cells by the neurosphere culture system.
► Proliferation was decreased after serial passages compared to the wild-type.
► Astrogenesis was promoted after serial passages compared to the wild-type.
► Pax6 is essential for the proliferation and differentiation of neural stem cells.