PUBLICATION

Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development

Authors
Ando, K., Shih, Y.H., Ebarasi, L., Grosse, A., Portman, D., Chiba, A., Mattonet, K., Gerri, C., Stainier, D.Y.R., Mochizuki, N., Fukuhara, S., Betsholtz, C., Lawson, N.D.
ID
ZDB-PUB-210728-39
Date
2021
Source
Developmental Biology   479: 11-22 (Journal)
Registered Authors
Betsholtz, Christer, Ebarasi, Lwaki, Lawson, Nathan, Mochizuki, Naoki, Stainier, Didier
Keywords
Mural cells, Pdgfrb, Pericytes, Vascular smooth muscle cells, Zebrafish
MeSH Terms
  • Myocytes, Smooth Muscle/metabolism
  • Proto-Oncogene Proteins c-sis/metabolism
  • Proto-Oncogene Proteins c-sis/physiology
  • Muscle, Smooth, Vascular/embryology
  • Muscle, Smooth, Vascular/metabolism*
  • Receptor, Platelet-Derived Growth Factor beta/genetics
  • Receptor, Platelet-Derived Growth Factor beta/metabolism*
  • Coronary Vessels/metabolism
  • Embryonic Development
  • Zebrafish Proteins/metabolism
  • Cell Differentiation
  • Pericytes/metabolism*
  • Signal Transduction/genetics
  • Zebrafish/embryology
  • Animals
(all 15)
PubMed
34310924 Full text @ Dev. Biol.
Abstract
Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle cells. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these zebrafish mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1059
    Point Mutation
    bns139
      Indel
      bns207
        Small Deletion
        ca8TgTransgenic Insertion
          la116TgTransgenic Insertion
            ncv1TgTransgenic Insertion
              ncv22TgTransgenic Insertion
                ncv25TgTransgenic Insertion
                  pd27TgTransgenic Insertion
                    s896TgTransgenic Insertion
                      1 - 10 of 14
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      pdgfbaCRISPR2-pdgfbaCRISPR
                      pdgfbbCRISPR2-pdgfbbCRISPR
                      1 - 2 of 2
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                      Fish
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      DsRed2EFGDsRed2
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      1 - 5 of 5
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                      Mapping
                      No data available