RRC ID 66023
Author Ando K, Wang W, Peng D, Chiba A, Lagendijk AK, Barske L, Crump JG, Stainier DYR, Lendahl U, Koltowska K, Hogan BM, Fukuhara S, Mochizuki N, Betsholtz C.
Title Peri-arterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling.
Journal Development
Abstract 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 naïve pdgfrblow mesenchymal cells. The emergence of peri-arterial pdgfrbhigh 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 pdgfrbhigh MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into pdgfrbhigh MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.
Volume 146(2)
Published 2019-1-25
DOI 10.1242/dev.165589
PII dev.165589
PMID 30642834
PMC PMC6919383
MeSH Animals Arteries / cytology* Arteries / embryology* Biomarkers / metabolism Body Patterning* Endothelium, Vascular / metabolism Mesoderm / embryology* Mesoderm / metabolism Receptor, Platelet-Derived Growth Factor beta / metabolism Receptors, Notch / metabolism* Signal Transduction* Time-Lapse Imaging Transforming Growth Factor beta / metabolism Zebrafish / embryology*
IF 5.611
Zebrafish Tg(UAS:GFP) Tg(UAS:RFP)