Jafree, DJ;
Moulding, D;
Kolatsi-Joannou, M;
Perretta Tejedor, N;
Price, KL;
Milmoe, NJ;
Walsh, CL;
... Long, DA; + view all
(2020)
Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease.
eLife
, 8
, Article e48183. 10.7554/eLife.48183.
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Abstract
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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