PUBLICATION

Peri-arterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling

Authors
Ando, K., Wang, W., Peng, D., Chiba, A., Lagendijk, A., Barske, L., Crump, J.G., Stainier, D.Y.R., Lendahl, U., Koltowska, K., Hogan, B.M., Fukuhara, S., Mochizuki, N., Betsholtz, C.
ID
ZDB-PUB-190116-4
Date
2019
Source
Development (Cambridge, England)   146(2): (Journal)
Registered Authors
Barske, Lindsey, Betsholtz, Christer, Crump, Gage DeKoeyer, Fukuhara, Shigetomo, Hogan, Ben M., Mochizuki, Naoki, Stainier, Didier
Keywords
Mural cells, Notch, Pericytes, Vascular smooth muscle cells, Zebrafish
MeSH Terms
  • 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*
PubMed
30642834 Full text @ Development
Abstract
Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms regulating MC development remain incompletely understood, particularly those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish utilizing 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 while 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.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes