TY - JOUR
T1 - Suppressor of fused controls perinatal expansion and quiescence of future dentate adult neural stem cells
AU - Noguchi, Hirofumi
AU - Castillo, Jesse Garcia
AU - Nakashima, Kinichi
AU - Pleasure, Samuel J.
N1 - Funding Information:
Uehara Memorial Foundation Hirofumi Noguchi Japan Society for the Promotion of Science Overseas Research Fellowship Hirofumi Noguchi Japan Science Society Sasakawa Scientific Research Grant Hirofumi Noguchi National Institutes of Health R01 NS075188 Samuel J Pleasure The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Funding Information:
We thank members of the SJP lab for helpful discussions, in particular OR Yabut and B Tran for technical help, suggestions, and helping to write this manuscript. This research was supported by NIH grant R01 NS075188 (SJP), Sasakawa Scientific Research Grant (HN), The Uehara Memorial Foundation (HN), JSPS Overseas Research Fellowships (HN).
Publisher Copyright:
© Noguchi et al.
PY - 2019/4/11
Y1 - 2019/4/11
N2 - Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, 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 by regulating Sonic Hedgehog (Shh) signaling activity. Deletion of Sufu in NSCs early in DG development decreases Shh signaling activity 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 enter a quiescent state 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 expansion and proper transition of NSC pools to quiescent states during DG development.
AB - Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, 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 by regulating Sonic Hedgehog (Shh) signaling activity. Deletion of Sufu in NSCs early in DG development decreases Shh signaling activity 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 enter a quiescent state 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 expansion and proper transition of NSC pools to quiescent states during DG development.
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U2 - 10.7554/eLife.42918
DO - 10.7554/eLife.42918
M3 - Article
C2 - 30973324
AN - SCOPUS:85064722649
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e42918
ER -