PUBLICATION
Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning
- Authors
- Rosa, A., Giese, W., Meier, K., Alt, S., Klaus-Bergmann, A., Edgar, L.T., Bartels, E., Collins, R., Szymborska, A., Coxam, B., Bernabeu, M.O., Gerhardt, H.
- ID
- ZDB-PUB-211222-8
- Date
- 2021
- Source
- Development (Cambridge, England) 149(3): (Journal)
- Registered Authors
- Collins, Russell, Coxam, Baptiste, Gerhardt, Holger, Meier, Katja, Rosa, Andre, Szymborska-Mell, Anna
- Keywords
- F-actin, Migration, Proliferation, Shear stress, Vessel remodelling, WASp
- MeSH Terms
-
- Actins/genetics
- Animals
- Arteries/growth & development
- Arteries/metabolism
- Blood Vessels/growth & development*
- Cell Movement/genetics
- Cell Proliferation/genetics
- Endothelial Cells/metabolism
- Gene Expression Regulation, Developmental/genetics
- Humans
- Intercellular Junctions/genetics
- Morphogenesis/genetics*
- Platelet Endothelial Cell Adhesion Molecule-1/genetics*
- Veins/growth & development
- Veins/metabolism
- Wiskott-Aldrich Syndrome Protein/genetics*
- Zebrafish/genetics
- Zebrafish/growth & development
- PubMed
- 34931661 Full text @ Development
Citation
Rosa, A., Giese, W., Meier, K., Alt, S., Klaus-Bergmann, A., Edgar, L.T., Bartels, E., Collins, R., Szymborska, A., Coxam, B., Bernabeu, M.O., Gerhardt, H. (2021) Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning. Development (Cambridge, England). 149(3):.
Abstract
Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are quantitatively coordinated to drive vascular network morphogenesis remains unknown. Here, using the zebrafish vasculature as a model system, we demonstrate that the balanced distribution of endothelial cells as well as the resulting regularity of vessel caliber, is a result of cell migration from veins towards arteries and cell proliferation in veins. We identify the Wiskott-Aldrich Syndrome protein (WASp) as an important molecular regulator of this process and show that loss of coordinated migration from veins to arteries upon wasb depletion results in aberrant vessel morphology and the formation of persistent arteriovenous shunts. We demonstrate that WASp achieves its function through the coordination of junctional actin assembly and PECAM1 recruitment and provide evidence that this is conserved in human. Overall, we demonstrate that functional vascular patterning in the zebrafish trunk is established through differential cell migration regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping