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

Document Type

Journal Article

Publication Date

5-1-2020

Journal

Nat Commun

Volume

11

Issue

1

DOI

10.1038/s41467-020-16028-8

Grant Information

5F32NS098647/U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

R01NS090383/U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

U54HD090257/U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

Comments

This is an open access PubMed Central article.

Peer Reviewed

1

Open Access

1

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