ZFIN ID: ZDB-PUB-190807-4
Cerebrovascular endothelial cells form transient Notch-dependent cystic structures in zebrafish
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.
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:
  • Actins/antagonists & inhibitors
  • Actins/genetics
  • Actins/metabolism
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/cytology*
  • Blood Vessels/embryology
  • Blood Vessels/metabolism
  • Blood Vessels/ultrastructure
  • Brain/blood supply
  • Brain/cytology*
  • Brain/embryology
  • Brain/metabolism
  • Bridged Bicyclo Compounds, Heterocyclic/pharmacology
  • Cerebrovascular Circulation/genetics
  • Embryo, Nonmammalian
  • Endothelial Cells/metabolism
  • Endothelial Cells/ultrastructure*
  • Gene Expression Regulation, Developmental*
  • Heterocyclic Compounds, 4 or More Rings/pharmacology
  • Myosin Type II/antagonists & inhibitors
  • Myosin Type II/genetics
  • Myosin Type II/metabolism
  • Neovascularization, Physiologic/genetics*
  • Nitric Oxide/metabolism
  • Organelles/metabolism
  • Organelles/ultrastructure
  • Polymerization/drug effects
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Thiazolidines/pharmacology
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 31379129 Full text @ EMBO Rep.
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.