Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Okasato R

PROVIDER: S-EPMC8564058 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Okasato Ryohei R Kano Kuniyuki K Kise Ryoji R Inoue Asuka A Fukuhara Shigetomo S Aoki Junken J

iScience 20211012 11

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 ...[more]

PMID: 34755093

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Project description:Background & aimsProliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein-coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis.MethodsIntestinal tissues from control (Gnaqflox/floxGna11+/+ ), Int-Gq knock-out (KO) (VilCre+/-Gnaqflox/floxGna11+/+ ), G11 KO (Gnaqflox/floxGna11-/- ), and Int-Gq/G11 double knock-out (DKO) (VilCre+/-Gnaqflox/floxGna11-/- ) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry. The effect of Gαq/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of Gαq/11 in colon.ResultsPaneth cells were enlarged, increased in number, and mislocalized in Int-Gq/G11 DKO small intestine. Paneth cells also reacted with PAS and Muc2 antibody, indicating an intermediate character of Paneth and goblet cells. The nuclear β-catenin, T-cell factor 1, and Sox9 expression were reduced severely in the crypt base of Int-Gq/G11 DKO intestine. Proliferation was activated in the crypt base and apoptosis was enhanced along the crypt. Int-Gq/G11 DKO mice were susceptible to DSS colitis. Proliferation was inhibited in the crypt of unaffected and regenerative areas. Cystic crypts, periodic acid-Schiff-positive cells, and Muc2-positive cells were unusually observed in the ulcerative region.ConclusionsThe Gαq/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/β-catenin signaling was reduced significantly in the crypt base in Gαq/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis.

Dataset Information

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

Publications

An ATX-LPA<sub>6</sub>-Gα<sub>13</sub>-ROCK axis shapes and maintains caudal vein plexus in zebrafish.

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