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Peri-arterial specification of vascular mural cells from naive mesenchyme requires Notch signaling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Natl Cerebral & Cardiovasc Ctr, Dept Cell Biol, Res Inst, Suita, Osaka, Japan.ORCID iD: 0000-0002-4152-5706
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld , Australia.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Natl Cerebral & Cardiovasc Ctr, Dept Cell Biol, Res Inst, Suita, Osaka , Japan.
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2019 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 146, no 2, article id UNSP dev165589Article in journal (Refereed) Published
Abstract [en]

Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using pdgfrb and abcc9 reporters, we show that the onset of expression of abcc9, a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in pdgfrb expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naive pdgfrb(low) mesenchymal cells. The emergence of peri-arterial pdgfrb(high) MCs required Notch signaling. We found that pdgfrb-positive cells express notch2 in addition to notch3, and although depletion of notch2 or notch3 failed to block MC emergence, embryos depleted of both notch2 and notch3 lost mesoderm- as well as neural crest-derived pdgfrb(high) MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into pdgfrb(high) MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.

Place, publisher, year, edition, pages
COMPANY BIOLOGISTS LTD , 2019. Vol. 146, no 2, article id UNSP dev165589
Keywords [en]
Mural cells, Pericytes, Vascular smooth muscle cells, Zebrafish, Notch
National Category
Cell and Molecular Biology Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-377362DOI: 10.1242/dev.165589ISI: 000457418100002PubMedID: 30642834OAI: oai:DiVA.org:uu-377362DiVA, id: diva2:1289906
Funder
Swedish Research Council, 2015-00550Swedish Research Council, 2016-01437EU, European Research Council, AdG294556Swedish Cancer Society, 150735Knut and Alice Wallenberg Foundation, 2015.0030Knut and Alice Wallenberg Foundation, 2017.0144Ragnar Söderbergs stiftelseAvailable from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved

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Ando, KojiPeng, DiKoltowska, KatarzynaBetsholtz, Christer

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