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Temporal modulation of collective cell behavior controls vascular network topology
oleh: Esther Kur, Jiha Kim, Aleksandra Tata, Cesar H Comin, Kyle I Harrington, Luciano da F Costa, Katie Bentley, Chenghua Gu
Format: | Article |
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Diterbitkan: | eLife Sciences Publications Ltd 2016-02-01 |
Deskripsi
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.