PUBLICATION
Combined forces of hydrostatic pressure and actin polymerization drive endothelial tip cell migration and sprouting angiogenesis
- Authors
- Kondrychyn, I., He, L., Wint, H., Betsholtz, C., Phng, L.K.
- ID
- ZDB-PUB-250221-6
- Date
- 2025
- Source
- eLIFE 13: (Journal)
- Registered Authors
- Betsholtz, Christer, Kondrychyn, Igor, Phng, Li-Kun
- Keywords
- actin, angiogenesis, aquaporin, cell migration, developmental biology, hydrostatic pressure, water flow, zebrafish
- Datasets
- GEO:GSE262232
- MeSH Terms
-
- Cell Movement*
- Actins*/metabolism
- Zebrafish*
- Angiogenesis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Polymerization*
- Animals
- Hydrostatic Pressure*
- Endothelial Cells*/metabolism
- Endothelial Cells*/physiology
- Neovascularization, Physiologic*
- PubMed
- 39977018 Full text @ Elife
Citation
Kondrychyn, I., He, L., Wint, H., Betsholtz, C., Phng, L.K. (2025) Combined forces of hydrostatic pressure and actin polymerization drive endothelial tip cell migration and sprouting angiogenesis. eLIFE. 13:.
Abstract
Cell migration is a key process in the shaping and formation of tissues. During sprouting angiogenesis, endothelial tip cells invade avascular tissues by generating actomyosin-dependent forces that drive cell migration and vascular expansion. Surprisingly, endothelial cells (ECs) can still invade if actin polymerization is inhibited. In this study, we show that endothelial tip cells employ an alternative mechanism of cell migration that is dependent on Aquaporin (Aqp)-mediated water inflow and increase in hydrostatic pressure. In the zebrafish, ECs express aqp1a.1 and aqp8a.1 in newly formed vascular sprouts in a VEGFR2-dependent manner. Aqp1a.1 and Aqp8a.1 loss-of-function studies show an impairment in intersegmental vessels formation because of a decreased capacity of tip cells to increase their cytoplasmic volume and generate membrane protrusions, leading to delayed tip cell emergence from the dorsal aorta and slower migration. Further inhibition of actin polymerization resulted in a greater decrease in sprouting angiogenesis, indicating that ECs employ two mechanisms for robust cell migration in vivo. Our study thus highlights an important role of hydrostatic pressure in tissue morphogenesis.
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Human Disease / Model
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