Wnt/β-catenin signalling is dispensable for adult neural stem cell homeostasis and activation
| Autor: | Lachlan Harris, Sophie H. L. Austin, François Guillemot, Rut Gabarró-Solanas, Piero Rigo, Oana Paun, Noelia Urbán |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Neurogenesis Stem Cells & Regeneration Stimulation Hippocampal formation Biology Quiescence Adult neurogenesis Hippocampus Transcriptome Wnt Mice Neural Stem Cells Animals Homeostasis Molecular Biology Wnt Signaling Pathway reproductive and urinary physiology beta Catenin Cell Proliferation Adult stem cells Neurons Wnt signaling pathway Cell Differentiation Stem Cells and Regeneration Neural stem cell Cell biology nervous system diseases nervous system Neural Development Female Stem cell biological phenomena cell phenomena and immunity Developmental Biology Adult stem cell |
| Zdroj: | Development (Cambridge, England) article-version (VoR) Version of Record |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | Adult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage, but whether it has a direct role in the regulation of NSCs remains unclear. Here, we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed the neuronal differentiation of proliferating NSCs and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, deletion of β-catenin in NSCs did not affect either their activation or maintenance of their stem cell characteristics. Together, these results indicate that, although NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which reconciles some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs. Summary: Wnt/β-catenin signalling stimulation promotes the exit from quiescence and differentiation of adult hippocampal neural stem cells but is dispensable for homeostatic neurogenesis in the dentate gyrus of young mice. |
| Databáze: | OpenAIRE |
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