4.7 Article

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

Journal

ISCIENCE
Volume 24, Issue 11, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2021.103254

Keywords

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Funding

  1. Leading Advanced Projects for Medical Innovation (LEAP) [JP18gm0010004h0002]
  2. Japan Agency for Medical Research and Development (AMED)
  3. KAKENHI [JP15H05899]

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The study found that the ATX-LPA(6) axis cooperates with blood flow to generate contractile force in endothelial cells, contributing to the formation and maintenance of the CVP.
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 LPA(6) receptor and downstream G alpha(13) showed the same phenotype. Administration of OMPT, a stable LPA-analog, induced rapid CVP constriction, which was attenuated significantly in the LPA(6) mutant. We also found that blood flow-induced CVP formation was dependent on ATX. The present study demonstrated that the ATX-LPA(6) axis acts cooperatively with blood flow and contributes to the formation and maintenance of the CVP by generating contractive force in endothelial cells.

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