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Nat Commun. 2018 Jan 2;9(1):36. doi: 10.1038/s41467-017-02440-0.

Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination.

Author information

1
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, 11794, USA.
2
Materials Science and Engineering, Stony Brook University, Stony Brook, NY, 11794, USA.
3
Eli & Edythe Broad Center of Regeneration Medicine & Stem Cell Research, University of California-San Francisco, San Francisco, CA, 94143, USA.
4
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY, 11794, USA.
5
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, 11794, USA. adan.aguirre@stonybrook.edu.

Abstract

Adult neural stem cells (NSCs) reside in a specialized microenvironment, the subventricular zone (SVZ), which provides them with unique signaling cues to control their basic properties and prevent their exhaustion. While the signaling mechanisms that regulate NSC lineage progression are well characterized, the molecular mechanisms that trigger the activation of quiescent NSCs during homeostasis and tissue repair are still unclear. Here, we uncovered that the NSC quiescent state is maintained by Rho-GTPase Cdc42, a downstream target of non-canonical Wnt signaling. Mechanistically, activation of Cdc42 induces expression of molecules involved in stem cell identity and anchorage to the niche. Strikingly, during a demyelination injury, downregulation of non-canonical Wnt-dependent Cdc42 activity is necessary to promote activation and lineage progression of quiescent NSCs, thereby initiating the process of tissue repair.

PMID:
29296000
PMCID:
PMC5750230
DOI:
10.1038/s41467-017-02440-0
[Indexed for MEDLINE]
Free PMC Article

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