Temporal modulation of collective cell behavior controls vascular network topology
Feb 24, 2016·,,,,,,,·
0 min read
Esther Kur
Jiha Kim
Aleksandra Tata
Cesar H Comin
Kyle I Harrington
Luciano Da F Costa
Katie Bentley
Chenghua Gu
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.
Type
Publication
eLife, 5(e13212)