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| Item Type: | Article |
|---|---|
| Title: | Temporal modulation of collective cell behavior controls vascular network topology |
| Creators Name: | Kur, E., Kim, J., Tata, A., Comin, C.H., Harrington, K.I., Costa, L.d.F., Bentley, K. and Gu, C. |
| 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. |
| Keywords: | Cell Proliferation, Computer Simulation, Endothelial Cells, Inbred C57BL Mice, Knockout Mice, Notch Receptors, Optical Imaging, Physiologic Neovascularization, Vascular Endothelial Growth Factor A, Animals, Mice |
| Source: | eLife |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications |
| Volume: | 5 |
| Page Range: | e13212 |
| Date: | 24 February 2016 |
| Official Publication: | https://doi.org/10.7554/eLife.13212 |
| PubMed: | View item in PubMed |
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