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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.

Original publication

DOI

10.1242/dev.095018

Type

Journal article

Journal

Development

Publication Date

08/2013

Volume

140

Pages

3335 - 3347

Keywords

Adult neural stem cell, Notch3, Quiescence, Animals, Animals, Genetically Modified, Brain, Cell Cycle, Cell Proliferation, Embryo, Nonmammalian, Gene Knockdown Techniques, Morpholinos, Neural Stem Cells, Neuroglia, Neurons, Receptor, Notch1, Receptor, Notch3, Receptors, Notch, Signal Transduction, Zebrafish, Zebrafish Proteins