Temporal modulation of collective cell behavior controls vascular network topology
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/13212 |
| _version_ | 1828375089951801344 |
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| author | Esther Kur Jiha Kim Aleksandra Tata Cesar H Comin Kyle I Harrington Luciano da F Costa Katie Bentley Chenghua Gu |
| author_facet | Esther Kur Jiha Kim Aleksandra Tata Cesar H Comin Kyle I Harrington Luciano da F Costa Katie Bentley Chenghua Gu |
| author_sort | Esther Kur |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:42:47Z |
| format | Article |
| id | doaj.art-e8d5328bc849497b9e4e7029d69992ff |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:42:47Z |
| publishDate | 2016-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e8d5328bc849497b9e4e7029d69992ff2022-12-22T02:05:27ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.13212Temporal modulation of collective cell behavior controls vascular network topologyEsther Kur0Jiha Kim1Aleksandra Tata2Cesar H Comin3Kyle I Harrington4Luciano da F Costa5Katie Bentley6Chenghua Gu7https://orcid.org/0000-0002-4212-7232Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesInstituto de Física de São Carlos, University of Sao Paulo, Sao Carlos, BrazilCenter for Vascular Biology Research, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United StatesInstituto de Física de São Carlos, University of Sao Paulo, Sao Carlos, BrazilCenter for Vascular Biology Research, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesVascular 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.https://elifesciences.org/articles/13212computational modelingtip celltemporal regulationvascular topologydelta-notchangiogensis |
| spellingShingle | Esther Kur Jiha Kim Aleksandra Tata Cesar H Comin Kyle I Harrington Luciano da F Costa Katie Bentley Chenghua Gu Temporal modulation of collective cell behavior controls vascular network topology eLife computational modeling tip cell temporal regulation vascular topology delta-notch angiogensis |
| title | Temporal modulation of collective cell behavior controls vascular network topology |
| title_full | Temporal modulation of collective cell behavior controls vascular network topology |
| title_fullStr | Temporal modulation of collective cell behavior controls vascular network topology |
| title_full_unstemmed | Temporal modulation of collective cell behavior controls vascular network topology |
| title_short | Temporal modulation of collective cell behavior controls vascular network topology |
| title_sort | temporal modulation of collective cell behavior controls vascular network topology |
| topic | computational modeling tip cell temporal regulation vascular topology delta-notch angiogensis |
| url | https://elifesciences.org/articles/13212 |
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