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Commentary & View

VEGF and Notch Signaling–The Yin and Yang of Angiogenic Sprouting

Mats Hellström, Li-Kun Phng and Holger Gerhardt

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Tubular sprouting in angiogenesis relies on division of labour between the endothelial tip cell, leading and guiding the sprout and their neighbouring stalk cells, which divide and form the vascular lumen. We previously learned how the graded extracellular distribution of heparin-binding Vascular Endothelial Growth Factor (VEGF)-A orchestrates and balances tip and stalk cell behaviour. Recent data now provided insight into the regulation of tip cell numbers, illustrating how Delta-like (Dll)4 – Notch signalling functions to limit the explorative tip cell behaviour induced by VEGF-A. These data also provided a first answer to the question why not all endothelial cells stimulated by VEGF-A turn into tip cells. Here we review this new model and discuss how VEGF-A and Dll4/Notch signalling may interact dynamically at cellular level to control vascular patterning.

Authors

Mats Hellström

AngioGenetics Sweden AB; Stockholm, Sweden; Department of Medical Biochemistry and Biophysics; Karolinska Institute Division of Matrix Biology; Stockholm Sweden

Li-Kun Phng

Vascular Biology Laborator; London Research Institute; Cancer Research UK; London UK

Holger Gerhardt

Vascular Biology Laboratory; Cancer Research UK; London Research Institute; London UK

This is an open-access article

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.