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Elife. 2019 Dec 6;8. pii: e48183. doi: 10.7554/eLife.48183.

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

Author information

1
Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
2
MB/PhD Programme, Faculty of Medical Sciences, University College London, London, United Kingdom.
3
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom.
4
UCL Institute of Ophthalmology, University College London, London, United Kingdom.
5
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, United States.
6
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
7
School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.
8
Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.

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.

KEYWORDS:

development; developmental biology; human; human biology; kidney; kidney disease; lymphatics; medicine; mouse; vessels

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