Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish

Author:

Ando Koji1,Fukuhara Shigetomo1,Izumi Nanae2,Nakajima Hiroyuki1,Fukui Hajime1,Kelsh Robert N.3,Mochizuki Naoki14

Affiliation:

1. Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

2. Frontier Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

3. Centre for Regenerative Medicine, Developmental Biology Programme, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK

4. AMED-CREST, National Cerebral and Cardiovascular Center, 5-7-1, Suita, Osaka, 565-8565, Japan

Abstract

Mural cells (MCs) consisting of vascular smooth muscle cells and pericytes cover the endothelial cells (ECs) to regulate vascular stability and homeostasis. Here, we clarified the mechanism how MCs develop and cover ECs by generating the transgenic zebrafish lines that allow live imaging of MCs and by lineage tracing in vivo. To cover cranial vessels, MCs derived from either neural crest cells or mesoderm emerged around the preformed EC tubes, proliferated and migrated along EC tubes. During their migration, the MCs moved forward by extending their processes along the inter-EC junctions, suggesting the role of inter-EC junctions as a scaffold for MC migration. In the trunk vasculature, MCs derived from mesoderm covered the ventral side of the dorsal aorta (DA), but not the posterior cardinal vein. Furthermore, the MCs migrating from the DA or emerging around intersegmental vessels (ISV) preferentially covered arterial ISVs rather than venous ISVs, indicating that MCs mostly cover arteries during vascular development. Thus, live imaging and lineage tracing enabled us to precisely clarify how MCs cover the EC tubes and to identify the origins of MCs.

Funder

Ministry of Education, Culture, Sports, Science, and Technology, Japan

Japan Society for the Promotion of Science

Ministry of Health, Labour and Welfare

Japan Agency for Medical Research and Development

Takeda Science Foundation

Naito Foundation

Mochida Memorial Foundation for Medical and Pharmaceutical Research

Medical Research Council

Daiichi Sankyo Foundation of Life Science

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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