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Related Experiment Video

Updated: Jun 8, 2026

Micropatterning and Assembly of 3D Microvessels

Micropatterning and Assembly of 3D Microvessels

Published on: September 9, 2016

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

Lars Jakobsson¹, Claudio A Franco, Katie Bentley

¹Vascular Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.

Nature Cell Biology

|September 28, 2010

Summary

Endothelial cells compete for tip cell position in sprouting angiogenesis via differential vascular endothelial growth factor receptor (VEGFR) levels. This competition, modulated by Notch signaling, dynamically reshuffles tip and stalk cell roles.

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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

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Area of Science:

Cell Biology
Developmental Biology
Biophysics

Background:

Sprouting angiogenesis involves coordinated endothelial cell behavior.
Notch and VEGFR signaling pathways regulate endothelial cell function.

Purpose of the Study:

Investigate the regulation and dynamics of endothelial cells during tip cell selection in sprouting angiogenesis.
Elucidate the roles of VEGFR and Notch signaling in tip cell competition.

Main Methods:

Computational modeling
Genetic mosaic sprouting assays (in vitro and in vivo)
Time-lapse microscopy imaging

Main Results:

Endothelial cells compete for tip cell position based on differential Vegfr1 and Vegfr2 levels.
Differential VEGFR levels influence tip selection only with functional Notch signaling by modulating Dll4 expression.
Dynamic position shuffling between tip and stalk cells was observed in vitro and in vivo.

Conclusions:

Differential VEGFR expression is a key mechanism for tip cell competition.
The VEGFR-Dll4-Notch signaling circuit is continuously re-evaluated through cell-cell interactions.
Dynamic tip cell exchange challenges traditional models of guided angiogenic sprouting.