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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717319319
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spelling 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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