Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone
Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activa...
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doaj-1d7b97039e0342b68859ae10b6f893502020-11-25T01:30:16ZengElsevierCell Reports2211-12472018-01-01224992100210.1016/j.celrep.2017.12.094Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular ZoneAnna Engler0Chiara Rolando1Claudio Giachino2Ichiko Saotome3Andrea Erni4Callum Brien5Runrui Zhang6Ursula Zimber-Strobl7Freddy Radtke8Spyros Artavanis-Tsakonas9Angeliki Louvi10Verdon Taylor11Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartments of Neurosurgery and Neuroscience, Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT 06520, USADepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandDepartment of Gene Vectors, Helmholtz Zentrum München, Marchioninistrasse 25, 81377 Munich, GermanyEPFL SV ISREC UPRAD, SV 2534 (Bâtiment SV), Station 19, 1015 Lausanne, SwitzerlandDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartments of Neurosurgery and Neuroscience, Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT 06520, USADepartment of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandNeurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ.http://www.sciencedirect.com/science/article/pii/S2211124717319319quiescenceneural stem cellsnicheneurogenesisolfactory bulbNotch |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Engler Chiara Rolando Claudio Giachino Ichiko Saotome Andrea Erni Callum Brien Runrui Zhang Ursula Zimber-Strobl Freddy Radtke Spyros Artavanis-Tsakonas Angeliki Louvi Verdon Taylor |
spellingShingle |
Anna Engler Chiara Rolando Claudio Giachino Ichiko Saotome Andrea Erni Callum Brien Runrui Zhang Ursula Zimber-Strobl Freddy Radtke Spyros Artavanis-Tsakonas Angeliki Louvi Verdon Taylor Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone Cell Reports quiescence neural stem cells niche neurogenesis olfactory bulb Notch |
author_facet |
Anna Engler Chiara Rolando Claudio Giachino Ichiko Saotome Andrea Erni Callum Brien Runrui Zhang Ursula Zimber-Strobl Freddy Radtke Spyros Artavanis-Tsakonas Angeliki Louvi Verdon Taylor |
author_sort |
Anna Engler |
title |
Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone |
title_short |
Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone |
title_full |
Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone |
title_fullStr |
Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone |
title_full_unstemmed |
Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone |
title_sort |
notch2 signaling maintains nsc quiescence in the murine ventricular-subventricular zone |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-01-01 |
description |
Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ. |
topic |
quiescence neural stem cells niche neurogenesis olfactory bulb Notch |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717319319 |
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