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Heterogeneity of lymphatic vessels during embryogenesis is critical for organ-specific lymphatic function. Little is known about lymphatics in the developing kidney, despite their established roles in pathology of the mature organ. We performed three-dimensional imaging to characterize lymphatic vessel formation in the mammalian embryonic kidney at single-cell resolution. In mouse, we visually and quantitatively assessed the development of kidney lymphatic vessels, remodeling from a ring-like anastomosis under the nascent renal pelvis; a site of VEGF-C expression, to form a patent vascular plexus. We identified a heterogenous population of lymphatic endothelial cell clusters in mouse and human embryonic kidneys. Exogenous VEGF-C expanded the lymphatic population in explanted mouse embryonic kidneys. Finally, we characterized complex kidney lymphatic abnormalities in a genetic mouse model of polycystic kidney disease. Our study provides novel insights into the development of kidney lymphatic vasculature; a system which likely has fundamental roles in renal development, physiology and disease.

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development, developmental biology, human, human biology, kidney, kidney disease, lymphatics, medicine, mouse, vessels, Animals, Gene Expression Regulation, Developmental, Genetic Heterogeneity, Humans, Kidney, Kinetics, Lymphangiogenesis, Lymphatic Vessels, Mammals, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Polycystic Kidney Diseases, Spatio-Temporal Analysis, Vascular Endothelial Growth Factor C