Embryonic Cortical Niche harbors heterogeneous Hes1 expressing neural stem cells varying in potency and lineage commitment

In the embryonic neural stem cell niche of the cortex, we characterized a heterogeneous pool of stem cells/progenitors composed of NIHes1 NSCs in addition to RGCs and IPCs using a Nestin-CreERT2;NIHes1fl/fl cKO mouse model. Our analyses show that NIHes1 NSCs are the precursor NSCs that produce RGCs and IPCs. Further, the loss of NIHes1 expression significantly alters the NSC niche, leading to increased gliogenesis and aberrant projection neuronal migration. The NIHes1 NSCs are set aside at embryonic stages as adult quiescent stem cells and upon activation, they are maintained by NIHes1 expression. In conclusion, NIHes1 NSCs are functionally distinct Hes1-expressing NSCs other than RGCs, which are critical for establishing the embryonic and adult NSC niches and, thereby, the overall cortical development.