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

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 (...

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Auteurs principaux: Ryohei Okasato, Kuniyuki Kano, Ryoji Kise, Asuka Inoue, Shigetomo Fukuhara, Junken Aoki
Format: article
Langue:EN
Publié: Elsevier 2021
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Accès en ligne:https://doaj.org/article/2cf2ab3e8a0a4343aebf61f02039d2ba
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Résumé: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.