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

Katrina L. Adams, Giulia Riparini, Payal Banerjee, Marjolein Breur, Marianna Bugiani, Vittorio Gallo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number2138
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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