Ando Koji, Fukuhara Shigetomo, Izumi Nanae, Nakajima Hiroyuki, Fukui Hajime, Kelsh Robert N, Mochizuki Naoki
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
Development. 2016 Apr 15;143(8):1328-39. doi: 10.1242/dev.132654. Epub 2016 Mar 7.
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 by which MCs develop and cover ECs by generating 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 a role for 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 (ISVs) 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 clarify precisely how MCs cover the EC tubes and to identify the origins of MCs.
由血管平滑肌细胞和周细胞组成的壁细胞覆盖在内皮细胞(ECs)上,以调节血管稳定性和体内平衡。在此,我们通过生成能够对壁细胞进行实时成像的转基因斑马鱼品系,并在体内进行谱系追踪,阐明了壁细胞发育并覆盖内皮细胞的机制。为了覆盖颅血管,源自神经嵴细胞或中胚层的壁细胞出现在预先形成的内皮细胞管周围,沿着内皮细胞管增殖并迁移。在迁移过程中,壁细胞通过沿着内皮细胞间连接延伸其突起向前移动,这表明内皮细胞间连接作为壁细胞迁移的支架发挥了作用。在躯干脉管系统中,源自中胚层的壁细胞覆盖了背主动脉(DA)的腹侧,但没有覆盖后主静脉。此外,从背主动脉迁移或在节间血管(ISVs)周围出现的壁细胞优先覆盖动脉节间血管而非静脉节间血管,这表明壁细胞在血管发育过程中主要覆盖动脉。因此,实时成像和谱系追踪使我们能够精确阐明壁细胞如何覆盖内皮细胞管,并确定壁细胞的起源。