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Peer-reviewedCC BY 4.0Development (Cambridge, England)

Blood flow coordinates collective endothelial cell migration during vascular plexus formation and promotes angiogenic sprout regression via flt4

  • Yan Chen1
  • Aaron M. Savage2
  • Zhen Jiang3,4
  • Ignacio Rodriguez-Pastrana2
  • Myles Wilson2
  • Hyejeong R. Kim5
  • Paul C. Evans6
  • Robert N. Wilkinson2
6 affiliations
  1. 1Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
  2. 2School of Life Sciences, Medical School, University of Nottingham, Nottingham, NG72UH, UK
  3. 3Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany
  4. 4German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim 61231, Germany
  5. 5Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK
  6. 6Centre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK
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Abstract

Nascent vascular networks adapt to the increasing metabolic demands of growing tissues by expanding via angiogenesis. As vascular networks expand, blood vessels remodel, progressively refining vascular connectivity to generate a more haemodynamically efficient network. This is driven by interplay between endothelial cell (EC) signalling and blood flow. While much is known about angiogenesis, less is understood of how blood flow remodels vessels. Here, we employ the zebrafish sub-intestinal venous plexus (SIVP) to characterise blood flow-dependent remodelling. Using live imaging to track ECs, we show that blood flow controls SIVP remodelling by coordinating collective EC migration within the developing plexus. Blood flow opposes continuous ventral EC migration within the SIVP and is required for angiogenic sprout regression to support plexus growth. Sprout regression occurs by coordinated migration of ECs from non-perfused leading sprouts, which migrate against blood flow and incorporate into the sub-intestinal vein. Sprout regression remains compatible with low blood flow but requires flt4 function under these conditions. Collectively, these studies reveal how blood flow sculpts a developing vascular plexus by coordinating EC migration and balancing vascular remodelling via flt4.

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Cite

BibTeXRIS
BibTeX
@article{chen2026blood,
  title = {{Blood flow coordinates collective endothelial cell migration during vascular plexus formation and promotes angiogenic sprout regression via flt4}},
  author = {Yan Chen and Aaron M. Savage and Zhen Jiang and Ignacio Rodriguez-Pastrana and Myles Wilson and Hyejeong R. Kim and Paul C. Evans and Robert N. Wilkinson},
  journal = {Development (Cambridge, England)},
  year = {2026},
  month = oct,
  doi = {10.1242/dev.205424},
  url = {https://doi.org/10.1242/dev.205424},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Blood flow coordinates collective endothelial cell migration during vascular plexus formation and promotes angiogenic sprout regression via flt4
AU  - Yan Chen
AU  - Aaron M. Savage
AU  - Zhen Jiang
AU  - Ignacio Rodriguez-Pastrana
AU  - Myles Wilson
AU  - Hyejeong R. Kim
AU  - Paul C. Evans
AU  - Robert N. Wilkinson
PY  - 2026
DA  - 2026/10/06
JO  - Development (Cambridge, England)
DO  - 10.1242/dev.205424
UR  - https://doi.org/10.1242/dev.205424
AB  - Nascent vascular networks adapt to the increasing metabolic demands of growing tissues by expanding via angiogenesis. As vascular networks expand, blood vessels remodel, progressively refining vascular connectivity to generate a more haemodynamically efficient network. This is driven by interplay between endothelial cell (EC) signalling and blood flow. While much is known about angiogenesis, less is understood of how blood flow remodels vessels. Here, we employ the zebrafish sub-intestinal venous plexus (SIVP) to characterise blood flow-dependent remodelling. Using live imaging to track ECs, we show that blood flow controls SIVP remodelling by coordinating collective EC migration within the developing plexus. Blood flow opposes continuous ventral EC migration within the SIVP and is required for angiogenic sprout regression to support plexus growth. Sprout regression occurs by coordinated migration of ECs from non-perfused leading sprouts, which migrate against blood flow and incorporate into the sub-intestinal vein. Sprout regression remains compatible with low blood flow but requires flt4 function under these conditions. Collectively, these studies reveal how blood flow sculpts a developing vascular plexus by coordinating EC migration and balancing vascular remodelling via flt4.
SN  - 0950-1991
SN  - 1477-9129
ER  -