Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2014 Apr;16(4):309-21. doi: 10.1038/ncb2926. Epub 2014 Mar 23.

The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis.

Author information

1
1] Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK [2].
2
Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK.
3
Centre for Computational Neuroscience and Robotics, Department of Informatics, University of Sussex, Brighton BN1 9QJ, UK.
4
Max-Planck-Institute for Molecular Biomedicine, Roentgenstr. 20 48149 Muenster, Germany.
5
Vascular Patterning Laboratory, VIB3-Vesalius Research Center & CMVB, Department of Oncology, KU Leuven Campus Gasthuisberg O&N4, Herestraat 49 box 912 B-3000 Leuven, Belgium.
6
Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskjöldsv. 20 751 85 Uppsala, Sweden.
7
1] Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK [2] Vascular Patterning Laboratory, VIB3-Vesalius Research Center & CMVB, Department of Oncology, KU Leuven Campus Gasthuisberg O&N4, Herestraat 49 box 912 B-3000 Leuven, Belgium.

Abstract

Endothelial cells show surprising cell rearrangement behaviour during angiogenic sprouting; however, the underlying mechanisms and functional importance remain unclear. By combining computational modelling with experimentation, we identify that Notch/VEGFR-regulated differential dynamics of VE-cadherin junctions drive functional endothelial cell rearrangements during sprouting. We propose that continual flux in Notch signalling levels in individual cells results in differential VE-cadherin turnover and junctional-cortex protrusions, which powers differential cell movement. In cultured endothelial cells, Notch signalling quantitatively reduced junctional VE-cadherin mobility. In simulations, only differential adhesion dynamics generated long-range position changes, required for tip cell competition and stalk cell intercalation. Simulation and quantitative image analysis on VE-cadherin junctional patterning in vivo identified that differential VE-cadherin mobility is lost under pathological high VEGF conditions, in retinopathy and tumour vessels. Our results provide a mechanistic concept for how cells rearrange during normal sprouting and how rearrangement switches to generate abnormal vessels in pathologies.

PMID:
24658686
DOI:
10.1038/ncb2926
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center