A Molecular Pathway for Arterial-Specific Association of Vascular Smooth Muscle Cells

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