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

DJ Jafree, D Moulding, M Kolatsi-Joannou… - Elife, 2019 - elifesciences.org
DJ Jafree, D Moulding, M Kolatsi-Joannou, N Perretta Tejedor, KL Price, NJ Milmoe…
Elife, 2019elifesciences.org
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 …
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.
eLife