title: Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium.
abstract: Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescence and increased occurrence of symmetric divisions. Expression analyses, morpholino-mediated invalidation and the generation of a notch3-null mutant directly implicate Notch3 in these effects. By contrast, abrogation of notch1b function results in the generation of neurons at the expense of the activated NSC state. Together, our results support a differential involvement of Notch receptors along the successive steps of NSC recruitment. They implicate Notch3 at the top of this hierarchy to gate NSC activation and amplification, protecting the homeostasis of adult NSC reservoirs under physiological conditions.
authors.affiliation: Institute of Neurobiology A. Fessard, Laboratory of Neurobiology and Development, CNRS UPR3294, Team Zebrafish Neurogenetics, Avenue de la Terrasse, Building 5, F-91198 Gif-sur-Yvette, France. alunni@inaf.cnrs-gif.fr
authors.forename: Alessandro
authors.initials: A
authors.lastname: Alunni
authors.forename: Monika
authors.initials: M
authors.lastname: Krecsmarik
authors.forename: Adriana
authors.initials: A
authors.lastname: Bosco
authors.forename: Sonya
authors.initials: S
authors.lastname: Galant
authors.forename: Luyuan
authors.initials: L
authors.lastname: Pan
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D060172:Morpholinos; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060172:Morpholinos; C561596:Notch1b protein, zebrafish; C520425:Notch3 protein, zebrafish; D051881:Receptor, Notch1; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D029961:Zebrafish Proteins
keywords: Adult neural stem cell; Notch3; Quiescence