1. Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium.
- Author
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Alunni A, Krecsmarik M, Bosco A, Galant S, Pan L, Moens CB, and Bally-Cuif L
- Subjects
- Animals, Animals, Genetically Modified genetics, Animals, Genetically Modified metabolism, Brain cytology, Brain metabolism, Embryo, Nonmammalian cytology, Embryo, Nonmammalian metabolism, Gene Knockdown Techniques, Morpholinos, Neural Stem Cells cytology, Neuroglia metabolism, Neurons cytology, Neurons metabolism, Receptor, Notch1 genetics, Receptor, Notch1 metabolism, Receptor, Notch3, Receptors, Notch genetics, Zebrafish genetics, Zebrafish metabolism, Zebrafish Proteins genetics, Cell Cycle, Cell Proliferation, Neural Stem Cells metabolism, Neuroglia cytology, Receptors, Notch metabolism, Signal Transduction, Zebrafish Proteins metabolism
- 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.
- Published
- 2013
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