Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting

Notch and vascular endothelial growth factor receptor (VEGFR) coordinates endothelial cells behaviour during angiogenesis sprouting although exactly how is uncertain. Endothelial cells dynamically compete for the leading position in a sprout through relative levels of Vegfr1 and Vegfr2 in a Notch de...

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Veröffentlicht in:Nature cell biology Jg. 12; H. 10; S. 943 - 953
Hauptverfasser: Jakobsson, Lars, Franco, Claudio A., Bentley, Katie, Collins, Russell T., Ponsioen, Bas, Aspalter, Irene M., Rosewell, Ian, Busse, Marta, Thurston, Gavin, Medvinsky, Alexander, Schulte-Merker, Stefan, Gerhardt, Holger
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.10.2010
Nature Publishing Group
Schlagworte:
631/114/2397
631/136/16
631/80/86
Angiogenesis
Animals
Biology
Biomedical and Life Sciences
Cancer Research
Cell Biology
Cells
Competition
Computational Biology
Computer Simulation
Developmental Biology
Drosophila
Drosophila - metabolism
Endothelial Cells - cytology
Endothelial Cells - metabolism
Genetic aspects
Insects
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Laboratories
Life Sciences
Ligands
Medical research
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Microscopy
Neovascularization, Physiologic - physiology
Physiological aspects
Receptors, Notch - metabolism
Retinal Vessels - metabolism
Signal Transduction
Stem Cells
Vascular endothelial growth factor
Vascular Endothelial Growth Factor Receptor-1 - metabolism
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Vertebrae
Zebrafish - embryology
United Kingdom > UK
ISSN:1465-7392, 1476-4679, 1476-4679
Online-Zugang:Volltext
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Zusammenfassung:Notch and vascular endothelial growth factor receptor (VEGFR) coordinates endothelial cells behaviour during angiogenesis sprouting although exactly how is uncertain. Endothelial cells dynamically compete for the leading position in a sprout through relative levels of Vegfr1 and Vegfr2 in a Notch dependent manner. Sprouting angiogenesis requires the coordinated behaviour of endothelial cells, regulated by Notch and vascular endothelial growth factor receptor (VEGFR) signalling. Here, we use computational modelling and genetic mosaic sprouting assays in vitro and in vivo to investigate the regulation and dynamics of endothelial cells during tip cell selection. We find that endothelial cells compete for the tip cell position through relative levels of Vegfr1 and Vegfr2 , demonstrating a biological role for differential Vegfr regulation in individual endothelial cells. Differential Vegfr levels affect tip selection only in the presence of a functional Notch system by modulating the expression of the ligand Dll4. Time-lapse microscopy imaging of mosaic sprouts identifies dynamic position shuffling of tip and stalk cells in vitro and in vivo , indicating that the VEGFR–Dll4–Notch signalling circuit is constantly re-evaluated as cells meet new neighbours. The regular exchange of the leading tip cell raises novel implications for the concept of guided angiogenic sprouting.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1465-7392
1476-4679
1476-4679
DOI:10.1038/ncb2103