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Updated: Jul 16, 2026
Mechanical Vessel Injury in Zebrafish Embryos
Published on: February 17, 2015
Disruption of Swell1/VRAC function impairs initial hemodynamics and activates compensatory leukotriene signaling in
Yen-Tzu Tseng1, Chia-Teng Chang1, Wei-Chun HuangFu2,3,4
1Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan.
Background:
Volume-regulated anion channels (VRACs) maintain cell-volume homeostasis, and SWELL1 is their essential subunit. Here, we show that VRAC/Swell1 also regulates initial hemodynamics and vascular development in zebrafish.
Results:
Stable swell1a and swell1b mutant zebrafish lines were established. In SWELL1- KO HAP1 cells, VRAC currents were rescued by wild-type, but not mutant, zebrafish swell1a or swell1b cDNA, confirming the alleles' loss-of-function nature. Microangiography and Tg(fli1a:eGFP) imaging revealed hypovolemia, reduced flow, and delayed vessel sprouting by 30 hpf, with severity proportional to allele dosage and partial recovery by 72 hpf. Whole-embryo transcriptomics highlighted upregulation of arachidonic-acid metabolism, especially the 5- lipoxygenase (5LO) axis. Pharmacological 5LO inhibition or the receptor cyslt1r knockdown aggravated circulatory defects, whereas leukotriene C4 treatment improved hemodynamics, indicating compensatory 5LO signalling. Thus, Swell1-dependent VRAC activity underpins embryonic hemodynamic stability, and 5LO-derived mediators partially buffer its loss.
Conclusion:
These findings link ion-channel function to lipid signalling in vascular development and suggest VRAC/Swell1-5LO cross-talk as a therapeutic target for blood-flow disorders.
