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

Jafree DJ., Moulding D., Kolatsi-Joannou M., Perretta Tejedor N., Price KL., Milmoe NJ., Walsh CL., Correra RM., Winyard PJ., Harris PC., Ruhrberg C., Walker-Samuel S., Riley PR., Woolf AS., Scambler P., Long DA.

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.

DOI

10.7554/elife.48183

Type

Journal article

Journal

eLife

Publication Date

06/12/2019

Volume

8

Addresses

Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Permalink Original publication