TABLE 3.
Quiescence promoting factors.
| Quiescence promoting factor | Model | Method | References |
| Notch (in general) | Mouse SGZ | Conditional knockout of RBPJk in Glast-expressing NSCs enhances neurogenesis (quiescence exit) and leads to NSC depletion 2 months after induction | Ehm et al., 2010 |
| Mouse SEZ | Conditional knockout of RBPJk in Nes-expressing NSCs enhances neurogenesis (quiescence exit) and leads to NSC depletion 3 months later | Imayoshi et al., 2010 | |
| Notch3 | Adult zebrafish pallium | Pharmacological blockade of gamma-secretase (Notch signaling pathway), notch3 mutant and notch3 MO show that Notch3 maintains quiescence | Alunni et al., 2013 |
| Mouse SEZ | Notch3-null mice and knockdown in adult with lentiviral expressing shRNA targeting Notch3 drive quiescence exit of NSCs, especially in the lateral and ventral wall | Kawai et al., 2017 | |
| Notch2 | Mouse SEZ | Conditional knockout of Notch2 in Hes5-expressing NSCs and short-term lineage tracing of Notch2-expressing cells shows that Notch2 maintains NSCs in quiescence, as loss of function leads to quiescence exit, increased neurogenesis and accelerated NSC exhaustion | Engler et al., 2018 |
| Mouse SGZ | Conditional knockout of Notch2 in Hes5-expressing NSCs leads to proliferation of NSCs and increased neurogenesis | Zhang et al., 2019 | |
| Dll1 | Mouse SEZ | Conditional knockout of Dll1 in Nes-expressing NSCs leads to quiescence exit (feedback to activate Notch in quiescent cells is not ensured anymore) | Kawaguchi et al., 2013 |
| Jagged1 | Mouse SGZ | Conditional knockout of Jagged1 in Nes-expressing NSCs leads to quiescence exit, implying that the interaction between Jagged1 and Notch is important for NSC quiescence and maintenance | Lavado and Oliver, 2014 |
| Fezf2 | Adult zebrafish pallium | Vivo-morpholino against fezf2 (short-term knock-down) leads to quiescence exit and increased proliferation | Berberoglu et al., 2014 |
| Bone morphogenic proteins | Mouse SEZ | BMP7 overexpression (virus-mediated) and Noggin expression (through protein purification or virus-mediated) show that expression of BMP maintains quiescence in type B cells/NSCs and therefore inhibits neurogenesis. It promotes the survival of type A progenitors | Lim et al., 2000 |
| Mouse SGZ | Blocking BMP through Noggin leads to reactivation and expansion of the NSC pool, suggesting that BMP is involved in quiescence control | Bonaguidi et al., 2008 | |
| Mouse SGZ | Intracerebral infusion of Noggin, lentivirus-mediated ablation of BMPR-1A and conditional knockout of Smad4 in Glast-expressing NSCs lead to quiescence exit, increased proliferation and exhaustion | Mira et al., 2010 | |
| NSCs derived from ESCs | NSC culture can be pushed to quiescence by adding BMP4 in 24 h | Martynoga et al., 2013 | |
| Inhibitors of DNA binding | Mouse SGZ | Conditional knockout of Id4 in Glast-expressing NSCs leads to increased ASCL1 expression and reactivation of previously quiescent NSCs | Blomfield et al., 2019 |
| Mouse SGZ | Conditional knockout of Id4 in Gfap-expressing cells using adeno-gfap::Cre viruses leads to NSC activation and cell-cycle entry without inducing neurogenesis | Zhang et al., 2019 | |
| NFIX | NSC culture derived from Mouse ESCs | Knockdown in vitro leads to impaired quiescence | Martynoga et al., 2013 |
| Mouse | NFIX-/- knockout: lethal at 3 weeks. Proportion of cycling NSCs is increased in the mutant. | Martynoga et al., 2013 | |
| Forkhead box O3 | Mouse SEZ and SGZ | Conditional knockout of FOXO1,3,4 in Gfap-expressing cells: decline of NSC pool and neurogenesis. | Paik et al., 2009 |
| Neurospheres from NSC culture | Neurospheres from FOXO3-/- versus FOXO3+/+, genome-wide microarray analysis: FoxO3 induces a program to preserve quiescence | Renault et al., 2009 | |
| Mouse SEZ and SGZ | FOXO3-/-: reduced number of NSCs in vivo (NSCs got activated and lost) | Renault et al., 2009 | |
| Adult mouse primary NSC culture | ChIP: FOXO3 binds proneural genes that are also targeted by Ascl1 possibly as a competitor to repress their expression and maintain NSC identity | Webb et al., 2013 | |
| Mouse SGZ | Conditional knockout of FoxO1,3,4 in Glast-expressing NSCs: leads to quiescence exit, increased proliferation followed by loss of NSC number | Schäffner et al., 2018 | |
| Mouse SEZ | FoxO3-/- knockout results in quiescence exit and increased neurogenesis | Webb et al., 2013 | |
| miR-9 | Zebrafish pallium | Vivo-MO targeting mature miR-9 leads to reactivation of previously quiescent mir-9+ NSCs. | Katz et al., 2016 |
| Gaba | Mouse postnatal SEZ, acute slices | GABAA-R-antagonist bicuculline leads to increase of proliferation in GFAP+ cells | Liu et al., 2005 |
| SGZ adult | Clonal analysis after cKO of gamma2-subunit-containing GABAA receptor in Nes-expressing NSCs – > quiescence exit and symmetrical self-renewal | Song et al., 2012 | |
| SGZ adult | Pharmacological inhibition – > increase of NSC proliferation Genetic deletion of GABAB1 (homozygous mutant) – > increase of NSC proliferation (Sox2+ cells) and differentiation to neuroblasts. Later loss of progenitors and increased neurogenesis | Giachino and Taylor, 2014 |