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Temporal modulation of collective cell behavior controls vascular network topology.
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2016 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 5Article in journal (Refereed) Epub ahead of print
Abstract [en]

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 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.

Place, publisher, year, edition, pages
2016. Vol. 5
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Bioinformatics and Systems Biology
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URN: urn:nbn:se:uu:diva-279467DOI: 10.7554/eLife.13212PubMedID: 26910011OAI: oai:DiVA.org:uu-279467DiVA: diva2:908135
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2017-11-30

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