Journal
DEVELOPMENT
Volume 148, Issue 20, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.199629
Keywords
Adult neurogenesis; Adult stem cells; Quiescence; Wnt
Categories
Funding
- UK Medical Research Council [FC001089]
- Wellcome Trust [FC001089]
- IMBA
- Austrian Academy of Sciences (OEAW)
- Austrian Science Fund [FWF: SFB-F78, SFB-F79, DOC72]
- Austrian Science Fund
- Francis Crick Institute - Cancer Research UK [FC001089]
- Francis Crick Institute
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Adult mouse hippocampal neural stem cells respond to Wnt/beta-catenin signaling, which can induce neuronal differentiation and activate or differentiate quiescent NSCs in a dose-dependent manner. However, the deletion of beta-catenin in NSCs does not affect their activation or maintenance of stem cell characteristics.
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/beta-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/beta-catenin reporters and transcriptomic data from in vivo and in vitro models to show that adult NSCs respond to Wnt/beta-catenin signalling. Wnt/beta-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 beta-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/beta-catenin stimulation in a dose-dependent and state-specific manner, Wnt/beta-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/beta-catenin signalling in adult hippocampal NSCs.
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