Endothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone

Nat Commun. 2020 May 1;11(1):2138. doi: 10.1038/s41467-020-16028-8.


Signaling molecules that regulate neurodevelopmental processes in the early postnatal subventricular zone (SVZ) are critical for proper brain development yet remain poorly characterized. Here, we report that Endothelin-1 (ET-1), a molecular component of the postnatal SVZ, promotes radial glial cell maintenance and proliferation in an autocrine manner via Notch signaling. Loss of ET-1 signaling increases neurogenesis and reduces oligodendrocyte progenitor cell proliferation (OPC) in the developing SVZ, thereby altering cellular output of the stem cell niche. We also show that ET-1 is required for increased neural stem cell and OPC proliferation in the adult mouse SVZ following demyelination. Lastly, high levels of ET-1 in the SVZ of patients with Cathepsin A-related arteriopathy with strokes and leukoencephalopathy correlate with an increased number of SVZ OPCs, suggesting ET-1's role as a regulator of glial progenitor proliferation may be conserved in humans. ET-1 signaling therefore presents a potential new therapeutic target for promoting SVZ-mediated cellular repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Nervous System / cytology*
  • Nervous System / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neuroglia / cytology*
  • Neuroglia / metabolism*
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology
  • Stem Cell Niche / genetics
  • Stem Cell Niche / physiology*


  • Endothelin-1
  • Receptors, Notch