Cited by 104Neurogenesis and neuroplasticity mechanismsCerebrospinal fluid and hydrocephalusIon channel regulation and function

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

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Petrik, David, Myoga, Michael H., Grade, Sofia, Gerkau, Niklas J., Pusch, Melanie, Rose, Christine R., Grothe, Benedikt, Götz, Magdalena·2018·Cell Stem Cell

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.

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Crossref · 10.1016/j.stem.2018.04.016

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Authors
Petrik, D., Myoga, M. H., Grade, S., Gerkau, N. J., Pusch, M., Rose, C. R., Grothe, B., & Götz, M.
Affiliations
  • Max Planck Institute of Neurobiology (DE)
  • Helmholtz Munich (DE)
  • Heinrich Heine University Düsseldorf (DE)
  • Munich Cluster for Systems Neurology (DE)
Corresponding author
Götz, Magdalena
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2018-06
Volume
22
Issue
6
Pages
865-878.e8
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2803588403
Cited by
104
References
93
Citations by year
2026: 7 · 2025: 10 · 2024: 12 · 2023: 7 · 2022: 8 · 2021: 16 · 2020: 25 · 2019: 15 · 2018: 4
FWCI
5.53
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • Site cant be reached (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • DFG
  • Marie Curie Fellowship (PIIF-GA-2013-628603)
  • DFG collaborative research center (SFB 870: Assembly and Function of Neuronal Circuits, CRC870/TP-A06, CRC870/TPB06)
  • German Excellence Initiative (Graduate School of Systemic Neurosciences, LMU, GSN 82, and EXC1010 Synergy)
  • priority program 1757 (Go13/1-2, Ro2327/8-2)
  • priority program 1738
  • advanced ERC grant (ChroNeuroRepair)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
epithelial sodium channel, adult neurogenesis, neural stem cells, subventricular zone, olfactory bulb, cell proliferation, cerebrospinal fluid flow, calcium signaling, calcium release-activated channels, ERK1/2 phosphorylation, ventricular fluid
MeSH terms
Animals, Cells, Cultured, Mice, Inbred C57BL, Mice, Knockout, Extracellular Fluid, Cell Proliferation, Mice, Epithelial Sodium Channels, Neural Stem Cells

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