Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.48183
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Funding
- Great Ormond Street Institute of Child Health
- University College London
- Medical Research Council [MR/P018629/1, MR/L002744/1, MR/K026739/1]
- British Heart Foundation [FS/19/14/34170, CH/11/1/28798, RG/15/14/31880]
- Diabetes UK [15/0005283]
- National Institute for Health Research [17DD08]
- Kidney Research UK [Paed_RP_10_2018, IN_012_2019]
- MRC [MR/S007687/1, MR/K026739/1, MR/P018629/1, MR/L002744/1] Funding Source: UKRI
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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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