Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease
- University College London, United Kingdom
- Mayo Clinic, United States
- University of Oxford, United Kingdom
- University of 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.
Data availability
The FIJI script used for segmenting and binarizing PROX1+/LYVE1+ cells has been provided as Source code file 1. All raw numerical data and results of statistical tests are attached as Source Data files with the appropriate figure.
Article and author information
Author details
Funding
UCL Great Ormond Street Institute of Child Health (Child Health Research Studentship)
- Daniyal J Jafree
- Peter Scambler
- David A Long
British Heart Foundation (RG/15/14/31880)
- Peter Scambler
Kidney Research UK (Paed_RP_10_2018)
- Daniyal J Jafree
- Adrian S Woolf
- David A Long
Kidney Research UK (IN_012_2019)
- Daniyal J Jafree
- David A Long
University College London MB/PhD Programme (MB/PhD Studentship)
- Daniyal J Jafree
Medical Research Council (MR/P018629/1)
- David A Long
Medical Research Council (MR/L002744/1)
- Adrian S Woolf
Medical Research Council (MR/K026739/1)
- Adrian S Woolf
British Heart Foundation (FS/19/14/34170)
- Rosa Maria Correra
Diabetes UK (15/0005283)
- David A Long
NIHR Great Ormond Street Hospital Biomedical Research Centre Award (17DD08)
- Dale Moulding
British Heart Foundation (CH/11/1/28798)
- Paul R Riley
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were carried out according to a UK Home Office project license (PPL: PE52D8C09) and were compliant with the UK Animals (Scientific Procedures) Act 1986.
Human subjects: Human fetal kidneys were obtained from the Human Developmental Biology Resource (http://www.hdbr.org), which obtains written consent from donors to collect, store and distribute human fetal material between 4-20PCW.
Reviewing Editor
- Kari Alitalo, Wihuri Research Institute, Finland
Version history
- Received: May 3, 2019
- Accepted: November 30, 2019
- Accepted Manuscript published: December 6, 2019 (version 1)
- Version of Record published: January 8, 2020 (version 2)
Copyright
© 2019, Jafree et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease
eLife 8:e48183.
https://doi.org/10.7554/eLife.48183
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