Hes1 overexpression leads to expansion of embryonic neural stem cell pool and stem cell reservoir in the postnatal brain

ABSTRACT Neural stem cells (NSCs) gradually alter their characteristics during mammalian neocortical development, resulting in the production of various neurons and glial cells, remain postnatal brain as a source adult neurogenesis. Notch-Hes signaling is key regulator cell properties developing brain, Hes1 major effector that strongly inhibits neuronal differentiation maintains NSCs. To manipulate expression levels NSCs, we generated transgenic (Tg) mice using Tet-On system. In Hes1-overexpressing Tg mice, NSCs were maintained both embryonic brains, generation later-born was prolonged until later stages neocortex. overexpression inhibited Tbr2+ intermediate progenitor but instead promoted basal radial glia-like subventricular zone (SVZ) at late stages. Furthermore, exhibited expansion enhanced neurogenesis SVZ brain. These results indicate expanded NSC pool led to reservoir