The preferential accumulation of vascular smooth muscle cells (vSMCs) on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. In zebrafish, the cxcr4a receptor (mammalian CXCR4) and its ligand cxcl12b (mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vSMCs during vascular development. We show that autocrine cxcl12b/cxcr4 activity leads to increased production of the vSMC chemoattractant ligand pdgfb by endothelial cells in vitro and increased expression of pdgfb by arteries of zebrafish and mice in vivo. Additionally, we demonstrate that expression of the blood flow-regulated transcription factor klf2a in primitive veins negatively regulates cxcr4/cxcl12 and pdgfb expression, restricting vSMC recruitment to the arterial vasculature. Together, this signalling axis leads to the differential acquisition of vSMCs at sites where klf2a expression is low and both cxcr4a and pdgfb are co-expressed, i.e. arteries during early development.

在早期发育过程中，血管平滑肌细胞（vSMC）相对于静脉的优先积累是一个已被充分描述的现象，但这种极化的分子途径尚不清楚。在斑马鱼中，cxcr4a受体（哺乳动物CXCR4）及其配体cxcl12b（哺乳动物CXCL12）都在与血管发育过程中第一个vSMC到达和分化一致的时间点优先在动脉上表达。我们显示自分泌cxcl12b / cxcr4活性导致体外内皮细胞增加vSMC趋化性配体pdgfb的产生并增加pdgfb的表达斑马鱼的动脉和小鼠体内。此外，我们证明了血流量调节的转录因子的表达klf2a在原始静脉负调节CXCR4 / CXCL12和PDGFB表达，限制VSMC募集到动脉脉管系统。总之，该信号转导轴导致在klf2a表达低且cxcr4a和pdgfb共同表达的位点（即早期发育的动脉）处的vSMC差异获取。