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

Manideep Chavali, Michael Klingener, Alexandros G. Kokkosis, Yury Garkun, Sylwia Felong, Arianna Maffei and Adan Aguirre ()
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Manideep Chavali: Stony Brook University
Michael Klingener: Stony Brook University
Alexandros G. Kokkosis: Stony Brook University
Yury Garkun: Stony Brook University
Sylwia Felong: Stony Brook University
Arianna Maffei: Stony Brook University
Adan Aguirre: Stony Brook University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02440-0

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