The role of the CXCL12/CXCR4 axis during embryonic lymphatic vascular development

Tyrosine kinase receptors and their cognate ligands are critical regulators of vascular endothelial cell proliferation and survival. However, less is known about the ability of the G protein-coupled receptor (GPCR) superfamily and their ligands to selectively shape the lymphatic vasculature in specific vessel beds or organs. The recently emerging roles of the chemokine receptor CXCR4 and its ligand CXCL12 in the formation of the cardiac and dermal arterial hierarchic vasculature, tip cell migration and lymph vessel guidance in mouse and zebrafish prompted us to revisit a potential function of the chemokine / receptor pair CXCL12 / CXCR4 during mouse lymphatic vessel development. We report here that the CXCL12 / CXCR4 axis is dispensable for the formation of the first primordial lymphatic structures, however, loss of Cxcr4 resulted in subtle differences in cell positioning during the formation of the dual contacts between the primordial thoracic duct (pTD) and the common cardinal vein and morphological changes in the nascent dermal lymphatics. We conclude that the CXCL12 / CXCR4 axis contributes to morphogenetic processes during fetal dermal lymphangiogenesis, but is dispensable for the initiation of lymphatic vessel development.