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Temporal modulation of collective cell behavior controls vascular network topology.

Publication ,  Journal Article
Kur, E; Kim, J; Tata, A; Comin, CH; Harrington, KI; Costa, LDF; Bentley, K; Gu, C
Published in: Elife
February 24, 2016

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.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

February 24, 2016

Volume

5

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Receptors, Notch
  • Optical Imaging
  • Neovascularization, Physiologic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Endothelial Cells
  • Computer Simulation
  • Cell Proliferation
  • Animals
 

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Kur, E., Kim, J., Tata, A., Comin, C. H., Harrington, K. I., Costa, L. D. F., … Gu, C. (2016). Temporal modulation of collective cell behavior controls vascular network topology. Elife, 5. https://doi.org/10.7554/eLife.13212
Kur, Esther, Jiha Kim, Aleksandra Tata, Cesar H. Comin, Kyle I. Harrington, Luciano da F. Costa, Katie Bentley, and Chenghua Gu. “Temporal modulation of collective cell behavior controls vascular network topology.Elife 5 (February 24, 2016). https://doi.org/10.7554/eLife.13212.
Kur E, Kim J, Tata A, Comin CH, Harrington KI, Costa LDF, et al. Temporal modulation of collective cell behavior controls vascular network topology. Elife. 2016 Feb 24;5.
Kur, Esther, et al. “Temporal modulation of collective cell behavior controls vascular network topology.Elife, vol. 5, Feb. 2016. Pubmed, doi:10.7554/eLife.13212.
Kur E, Kim J, Tata A, Comin CH, Harrington KI, Costa LDF, Bentley K, Gu C. Temporal modulation of collective cell behavior controls vascular network topology. Elife. 2016 Feb 24;5.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

February 24, 2016

Volume

5

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Receptors, Notch
  • Optical Imaging
  • Neovascularization, Physiologic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Endothelial Cells
  • Computer Simulation
  • Cell Proliferation
  • Animals