Temporal modulation of collective cell behavior controls vascular network topology

Details

• Alternative Title:
  eLife
• Personal Author:
  Kur, Esther ; Kim, Jiha ; Tata, Aleksandra ; Comin, Cesar H ; Harrington, Kyle I ; Costa, Luciano da F ; Bentley, Katie ; Gu, Chenghua
• 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.
• Subjects:
  Angiogensis Computational And Systems Biology Computational Modeling Delta-notch Developmental Biology And Stem Cells Mouse Other Short Report Temporal Regulation Tip Cell Vascular Topology

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• Source:
  eLife. 2016; 5.
• Pubmed ID:
  26910011
• Pubmed Central ID:
  PMC4811760
• Document Type:
  Journal Article
• Funding:
  DP1 NS092473/NS/NINDS NIH HHS/United States ; R01NS064583/NS/NINDS NIH HHS/United States ; DP1 NS092473/DP/NCCDPHP CDC HHS/United States ; R01 NS064583/NS/NINDS NIH HHS/United States ; T32 NS007484/NS/NINDS NIH HHS/United States
• Volume:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:dd5826869a162b75349e9cc84c3f7abd2b7f0ea55437839a221d8518a337a334
• Download URL:
  https://stacks.cdc.gov/view/cdc/41025/cdc_41025_DS1.pdf
• File Type:
  [PDF - 4.09 MB ]