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Temporal modulation of collective cell behavior controls vascular network topology

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Item Type:Article
Title:Temporal modulation of collective cell behavior controls vascular network topology
Creators Name:Kur, E. and Kim, J. and Tata, A. and Comin, C.H. and Harrington, K.I. and Costa, L.d.F. and Bentley, K. and Gu, C.
Abstract:Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by the VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedback loop, a previously unexplored dimension, is the key mechanism to determine vascular density. Iterating between computational modeling and in vivo live imaging, we demonstrate that the rate of tip-cell selection determines the length of linear sprout extension at the expense of branching, dictating network density. We provide the first example of a host tissue-derived signal (Semaphorin3E-Plexin-D1) that accelerates tip cell selection rate, yielding a dense network. We propose that temporal regulation of this critical, iterative aspect of network formation could be a general mechanism, and additional temporal regulators may exist to sculpt vascular topology.
Keywords:Cell Proliferation, Computer Simulation, Endothelial Cells, Inbred C57BL Mice, Knockout Mice, Notch Receptors, Optical Imaging, Physiologic Neovascularization, Vascular Endothelial Growth Factor A, Animals, Mice
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications
Volume:5
Page Range:e13212
Date:24 February 2016
Official Publication:https://doi.org/10.7554/eLife.13212
PubMed:View item in PubMed

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