Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease

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. Here, we harnessed three-dimensional imaging to characterize lymphatic formation in the mammalian embryonic kidney at single-cell resolution. In mouse, we visually and quantitatively assessed the development of kidney lymphatic vessels, first appearing as a ring-like anastomosis under the nascent renal pelvis and later remodeling into a patent vascular plexus. We discovered a heterogenous population of lymphatic endothelial cell clusters in mouse and human embryonic kidneys. Moreover, exogenous VEGF-C expanded the lymphatic population in explanted mouse embryonic kidneys. Finally, we identified 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; an understudied system which likely has fundamental roles in renal development, physiology and disease.