PUBLICATION

Cerebrovascular endothelial cells form transient Notch-dependent cystic structures in zebrafish

Authors
Kugler, E.C., van Lessen, M., Daetwyler, S., Chhabria, K., Savage, A.M., Silva, V., Plant, K., MacDonald, R.B., Huisken, J., Wilkinson, R.N., Schulte-Merker, S., Armitage, P., Chico, T.J.
ID
ZDB-PUB-190807-4
Date
2019
Source
EMBO reports   20: e47047 (Journal)
Registered Authors
Chico, Tim J., Huisken, Jan, MacDonald, Ryan, Schulte-Merker, Stefan, Wilkinson, Robert
Keywords
VEGF, Notch, Wnt, angiogenesis, endothelial cell, zebrafish
MeSH Terms
  • Embryo, Nonmammalian
  • Myosin Type II/antagonists & inhibitors
  • Myosin Type II/genetics
  • Myosin Type II/metabolism
  • Bridged Bicyclo Compounds, Heterocyclic/pharmacology
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Actins/antagonists & inhibitors
  • Actins/genetics
  • Actins/metabolism
  • Gene Expression Regulation, Developmental*
  • Animals, Genetically Modified
  • Thiazolidines/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Polymerization/drug effects
  • Blood Vessels/cytology*
  • Blood Vessels/embryology
  • Blood Vessels/metabolism
  • Blood Vessels/ultrastructure
  • Organelles/metabolism
  • Organelles/ultrastructure
  • Signal Transduction
  • Endothelial Cells/metabolism
  • Endothelial Cells/ultrastructure*
  • Nitric Oxide/metabolism
  • Brain/blood supply
  • Brain/cytology*
  • Brain/embryology
  • Brain/metabolism
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism
  • Animals
  • Cerebrovascular Circulation/genetics
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Heterocyclic Compounds, 4 or More Rings/pharmacology
  • Neovascularization, Physiologic/genetics*
(all 41)
PubMed
31379129 Full text @ EMBO Rep.
Abstract
We identify a novel endothelial membrane behaviour in transgenic zebrafish. Cerebral blood vessels extrude large transient spherical structures that persist for an average of 23 min before regressing into the parent vessel. We term these structures "kugeln", after the German for sphere. Kugeln are only observed arising from the cerebral vessels and are present as late as 28 days post fertilization. Kugeln do not communicate with the vessel lumen and can form in the absence of blood flow. They contain little or no cytoplasm, but the majority are highly positive for nitric oxide reactivity. Kugeln do not interact with brain lymphatic endothelial cells (BLECs) and can form in their absence, nor do they perform a scavenging role or interact with macrophages. Inhibition of actin polymerization, Myosin II, or Notch signalling reduces kugel formation, while inhibition of VEGF or Wnt dysregulation (either inhibition or activation) increases kugel formation. Kugeln represent a novel Notch-dependent NO-containing endothelial organelle restricted to the cerebral vessels, of currently unknown function.
Genes / Markers
Figures
No images available
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu7135TgTransgenic Insertion
    i149TgTransgenic Insertion
      i186TgTransgenic Insertion
        lcr1TgTransgenic Insertion
          md13TgTransgenic Insertion
            s916TgTransgenic Insertion
              s940TgTransgenic Insertion
                sd2TgTransgenic Insertion
                  sh467TgTransgenic Insertion
                    ubs1TgTransgenic Insertion
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      ccbe1MO1-ccbe1MRPHLNO
                      dll4MO5-dll4MRPHLNO
                      jag1bMO1-jag1bMRPHLNO
                      notch1bMO6-notch1bMRPHLNO
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 5 of 5
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      mCherryEFGmCherry
                      mCloverEFGmClover
                      NTREFGNTR
                      VenusEFGVenus
                      1 - 8 of 8
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                      Mapping
                      No data available
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                      Citation
                      Kugler, E.C., van Lessen, M., Daetwyler, S., Chhabria, K., Savage, A.M., Silva, V., Plant, K., MacDonald, R.B., Huisken, J., Wilkinson, R.N., Schulte-Merker, S., Armitage, P., Chico, T.J. (2019) Cerebrovascular endothelial cells form transient Notch-dependent cystic structures in zebrafish. EMBO reports. 20:e47047.