Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone

Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zon...

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Main Authors: Mathieu Daynac, Linda Tirou, Hélène Faure, Marc-André Mouthon, Laurent R. Gauthier, Heidi Hahn, François D. Boussin, Martial Ruat
Format: Article
Language:English
Published: Elsevier 2016-10-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671116301837
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author Mathieu Daynac
Linda Tirou
Hélène Faure
Marc-André Mouthon
Laurent R. Gauthier
Heidi Hahn
François D. Boussin
Martial Ruat
author_facet Mathieu Daynac
Linda Tirou
Hélène Faure
Marc-André Mouthon
Laurent R. Gauthier
Heidi Hahn
François D. Boussin
Martial Ruat
author_sort Mathieu Daynac
collection DOAJ
description Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ), one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ. The pool of non-neurogenic astrocytes was not modified, whereas the activated NSC pool increased after a short period, before progressively becoming exhausted. We also showed that Sonic Hedgehog regulates proliferation of activated NSCs in vivo and shortens both their G1 and S-G2/M phases in culture. These data demonstrate that Hh orchestrates the balance between quiescent and activated NSCs, with important implications for understanding adult neurogenesis under normal homeostatic conditions or during injury.
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spelling doaj.art-27a6e426bd4940a6a9431b0a9d15ec0e2022-12-21T19:28:29ZengElsevierStem Cell Reports2213-67112016-10-017473574810.1016/j.stemcr.2016.08.016Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular ZoneMathieu Daynac0Linda Tirou1Hélène Faure2Marc-André Mouthon3Laurent R. Gauthier4Heidi Hahn5François D. Boussin6Martial Ruat7CNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, FranceCNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, FranceCNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, FranceCEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, FranceCEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, FranceTumor Genetics Group, Institute of Human Genetics, University Medical Center, 37073 Göttingen, GermanyCEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, FranceCNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, FranceIdentifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ), one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ. The pool of non-neurogenic astrocytes was not modified, whereas the activated NSC pool increased after a short period, before progressively becoming exhausted. We also showed that Sonic Hedgehog regulates proliferation of activated NSCs in vivo and shortens both their G1 and S-G2/M phases in culture. These data demonstrate that Hh orchestrates the balance between quiescent and activated NSCs, with important implications for understanding adult neurogenesis under normal homeostatic conditions or during injury.http://www.sciencedirect.com/science/article/pii/S2213671116301837
spellingShingle Mathieu Daynac
Linda Tirou
Hélène Faure
Marc-André Mouthon
Laurent R. Gauthier
Heidi Hahn
François D. Boussin
Martial Ruat
Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
Stem Cell Reports
title Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
title_full Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
title_fullStr Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
title_full_unstemmed Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
title_short Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone
title_sort hedgehog controls quiescence and activation of neural stem cells in the adult ventricular subventricular zone
url http://www.sciencedirect.com/science/article/pii/S2213671116301837
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