(148a) Dynamics of Collective Endothelial Cell Migration in Response to Fluid Shear Stress

The endothelial cells that line blood and lymphatic vessels undergo complex, collective migration and rearrangement processes during embryonic development, and are known to be exquisitely responsive to fluid flow. At present, the molecular mechanisms by which endothelial cells sense fluid flow remain incompletely understood. Here, we report that both the G-protein-coupled receptor sphingosine 1-phosphate receptor 1 (S1PR1) and its ligand sphingosine 1-phosphate (S1P) are required for the collective upstream migration of human lymphatic endothelial cells. These findings are consistent with a model in which S1P and fluid flow act synergistically to guide development and remodeling in the lymphatic circulatory system.