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An ATX-LPA6-Gα13-ROCK axis shapes and maintains caudal vein plexus in zebrafish

ABSTRACT: Summary Lysophosphatidic acid (LPA) is a potential regulator of vascular formation derived from blood. In this study, we utilized zebrafish as a model organism to monitor the blood vessel formation in detail. Zebrafish mutant of ATX, an LPA-producing enzyme, had a defect in the caudal vein plexus (CVP). Pharmacological inhibition of ATX resulted in a fusion of the delicate vessels in the CVP to form large sac-like vessels. Mutant embryos of LPA6 receptor and downstream Gα13 showed the same phenotype. Administration of OMPT, a stable LPA-analog, induced rapid CVP constriction, which was attenuated significantly in the LPA6 mutant. We also found that blood flow-induced CVP formation was dependent on ATX. The present study demonstrated that the ATX-LPA6 axis acts cooperatively with blood flow and contributes to the formation and maintenance of the CVP by generating contractive force in endothelial cells. Graphical abstract Highlights • Blocking an ATX-LPA6-Gα13-ROCK axis causes malformation of the caudal vein plexus• The axis also contributes to maintaining the fine structure of the caudal vein plexus• Activation of LPA6 induces vasoconstriction• Caudal vein plexus formation evoked by blood flow is dependent on an ATX-LPA6 axis Cell biology; Developmental biology

SUBMITTER: Okasato R

PROVIDER: S-EPMC8564058 | biostudies-literature |

REPOSITORIES: biostudies-literature

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