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 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 G1and 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.
CNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Mathieu
M
Daynac
CNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Linda
L
Tirou
CNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Hélène
H
Faure
CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, France; INSERM, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Sud, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Diderot, Sorbonne Paris Cité, UMR 967, 92265 Fontenay-aux-Roses, France.
Marc-André
MA
Mouthon
CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, France; INSERM, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Sud, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Diderot, Sorbonne Paris Cité, UMR 967, 92265 Fontenay-aux-Roses, France.
Laurent R
LR
Gauthier
Tumor Genetics Group, Institute of Human Genetics, University Medical Center, 37073 Göttingen, Germany.
Heidi
H
Hahn
CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, 92265 Fontenay-aux-Roses, France; INSERM, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Sud, UMR 967, 92265 Fontenay-aux-Roses, France; Université Paris Diderot, Sorbonne Paris Cité, UMR 967, 92265 Fontenay-aux-Roses, France. Electronic address: boussin@cea.fr.
François D
FD
Boussin
CNRS, UMR-9197, Neuroscience Paris-Saclay Institute, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France. Electronic address: ruat@inaf.cnrs-gif.fr.
Martial
M
Ruat
D000818:Animals; D002453:Cell Cycle; D017353:Gene Deletion; D053823:Hedgehog Proteins / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons; D000072079:Patched Receptors / Q000235:genetics; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction; D055153:Stem Cell Niche
D053823:Hedgehog Proteins; D000072079:Patched Receptors
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