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Cell Stem Cell. 2018 Jun 1;22(6):865-878.e8. doi: 10.1016/j.stem.2018.04.016. Epub 2018 May 17.

Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner.

Author information

1
Division of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universitaet Munich, Planegg-Martinsried 82152, Germany; Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Oberschleissheim 85764, Germany.
2
Division of Neurobiology, Ludwig-Maximilians-Universitaet Munich, Planegg-Martinsried 82152, Germany; Max Planck Institute of Neurobiology, Planegg-Martinsried 82152, Germany.
3
Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, Duesseldorf 40225, Germany.
4
Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Oberschleissheim 85764, Germany.
5
Division of Neurobiology, Ludwig-Maximilians-Universitaet Munich, Planegg-Martinsried 82152, Germany; Max Planck Institute of Neurobiology, Planegg-Martinsried 82152, Germany; SYNERGY, Excellence Cluster of Systems Neurology, Biomedical Center, Ludwig-Maximilians-Universitaet, Munich, Germany.
6
Division of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universitaet Munich, Planegg-Martinsried 82152, Germany; Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Oberschleissheim 85764, Germany; SYNERGY, Excellence Cluster of Systems Neurology, Biomedical Center, Ludwig-Maximilians-Universitaet, Munich, Germany. Electronic address: magdalena.goetz@helmholtz-muenchen.de.

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.

KEYWORDS:

ENaC; adult neurogenesis; fluid flow; neural stem cells; proliferation

PMID:
29779889
DOI:
10.1016/j.stem.2018.04.016

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