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

Ryohei Okasato; Kuniyuki Kano; Ryoji Kise; Asuka Inoue; Shigetomo Fukuhara; Junken Aoki

doi:10.1016/j.isci.2021.103254

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

iScience. 2021 Oct 12;24(11):103254. doi: 10.1016/j.isci.2021.103254. eCollection 2021 Nov 19.

Authors

Ryohei Okasato^{1

2

3}, Kuniyuki Kano^{1

2

3}, Ryoji Kise², Asuka Inoue^{2

3}, Shigetomo Fukuhara⁴, Junken Aoki^{1

2

3}

Affiliations

¹ Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
³ AMED-LEAP, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
⁴ Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.

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.

Keywords: Cell biology; Developmental biology.