Temporal modulation of collective cell behavior controls vascular network topology.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kur, E; Kim, J; Tata, A; Comin, CH; Harrington, KI; Costa, LDF; Bentley, K; Gu, C

Published Date

  • February 24, 2016

Published In

Volume / Issue

  • 5 /

PubMed ID

  • 26910011

Pubmed Central ID

  • PMC4811760

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.13212

Language

  • eng

Conference Location

  • England