| First Author | Kur E | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 26910011 | Mgi Jnum | J:269685 |
| Mgi Id | MGI:6203790 | Doi | 10.7554/eLife.13212 |
| Citation | Kur E, et al. (2016) Temporal modulation of collective cell behavior controls vascular network topology. Elife 5:e13212 |
| abstractText | 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. |
