PUBLICATION

Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo

Authors
Gebala, V., Collins, R., Geudens, I., Phng, L.K., Gerhardt, H.
ID
ZDB-PUB-170214-33
Date
2016
Source
Nature cell biology   18: 443-50 (Journal)
Registered Authors
Collins, Russell, Gerhardt, Holger
Keywords
Actin, Angiogenesis, Myosin, Zebrafish
MeSH Terms
  • Actomyosin/metabolism
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/cytology
  • Blood Vessels/embryology*
  • Blood Vessels/metabolism
  • Endothelial Cells/metabolism
  • Female
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Morphogenesis*
  • Neovascularization, Physiologic*
  • Regional Blood Flow
  • Time-Lapse Imaging
  • Zebrafish
PubMed
26928868 Full text @ Nat. Cell Biol.
Abstract
How vascular tubes build, maintain and adapt continuously perfused lumens to meet local metabolic needs remains poorly understood. Recent studies showed that blood flow itself plays a critical role in the remodelling of vascular networks, and suggested it is also required for the lumenization of new vascular connections. However, it is still unknown how haemodynamic forces contribute to the formation of new vascular lumens during blood vessel morphogenesis. Here we report that blood flow drives lumen expansion during sprouting angiogenesis in vivo by inducing spherical deformations of the apical membrane of endothelial cells, in a process that we have termed inverse blebbing. We show that endothelial cells react to these membrane intrusions by local and transient recruitment and contraction of actomyosin, and that this mechanism is required for single, unidirectional lumen expansion in angiogenic sprouts. Our work identifies inverse membrane blebbing as a cellular response to high external pressure. We show that in the case of blood vessels such membrane dynamics can drive local cell shape changes required for global tissue morphogenesis, shedding light on a pressure-driven mechanism of lumen formation in vertebrates.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping