Suppressor of Fused controls perinatal expansion and quiescence of future dentate adult neural stem cells

Abstract

Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. The establishment and maintenance of quiescent NSC pools during development is not understood. Here we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development through regulation of Sonic Hedgehog (Shh) signaling. Deletion of Sufuin NSCs at the beginning of DG development decreases Shh signaling leading to reduced proliferation of NSCs, resulting in a small quiescent NSC pool in adult mice. We found that putative adult NSCs proliferate and increase their numbers in the first postnatal week and subsequently become quiescent towards the end of the first postnatal week. In the absence of Sufu, postnatal expansion of NSCs is compromised, and NSCs prematurely become quiescent. Thus, Sufu is required for Shh signaling activity ensuring the expansion and proper transition of NSC pools to quiescence during DG development.