Endothelial Ca2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo
Abstract
Sprouting angiogenesis is a well-coordinated process controlled by multiple extracellular inputs, including vascular endothelial growth factor (VEGF). However, little is known about when and how individual endothelial cell (EC) responds to angiogenic inputs in vivo. Here, we visualized endothelial Ca2+ dynamics in zebrafish and found that intracellular Ca2+ oscillations occurred in ECs exhibiting angiogenic behavior. Ca2+ oscillations depended upon Vegfr2 and Vegfr3 in ECs budding from the dorsal aorta (DA) and posterior cardinal vein, respectively. Thus, visualizing Ca2+ oscillations allowed us to monitor EC responses to angiogenic cues. Vegfr-dependent Ca2+ oscillations occurred in migrating tip cells as well as stalk cells budding from the DA. We investigated how Dll4/Notch signaling regulates endothelial Ca2+ oscillations and found that it was required for the selection of single stalk cell as well as tip cell. Thus, we captured spatio-temporal Ca2+ dynamics during sprouting angiogenesis, as a result of cellular responses to angiogenic inputs.
Article and author information
Author details
Reviewing Editor
- Janet Rossant, University of Toronto, Canada
Ethics
Animal experimentation: Animal experimentation: The experiments using zebrafish were approved by the animal committee of National Cerebral and Cardiovascular Center (No. 14005) and performed according to the guidance of the Institute.
Version history
- Received: May 18, 2015
- Accepted: November 19, 2015
- Accepted Manuscript published: November 20, 2015 (version 1)
- Version of Record published: December 31, 2015 (version 2)
Copyright
© 2015, Yokota et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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