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Epithelial sodium channel regulates adult neural stem cell proliferation in a flow-dependent manner

Petrik, David, Myoga, Michael H., Grade, Sofia, Gerkau, Niklas J., Pusch, Melanie, Rose, Christine R., Grothe, Benedikt and Götz, Magdalena 2018. Epithelial sodium channel regulates adult neural stem cell proliferation in a flow-dependent manner. Cell Stem Cell 22 (6) , 865-878.e8. 10.1016/j.stem.2018.04.016

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Abstract

One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier (Cell Press)
ISSN: 1934-5909
Date of First Compliant Deposit: 10 September 2019
Date of Acceptance: 17 April 2018
Last Modified: 03 Jun 2020 15:17
URI: http://orca-mwe.cf.ac.uk/id/eprint/125390

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