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

Daniyal J. Jafree, Dale Moulding, Maria Kolatsi-Joannou, Nuria Perretta Tejedor, Karen L. Price, Natalie Milmoe, Claire Walsh, Rosa Maria Correra, Paul J.D. Winyard, Peter C. Harris, Christiana Ruhrberg, Simon Walker-Samuel, Paul R. Riley, Adrian S. Woolf, Peter J. Scambler, David A. Long

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere48183
JournaleLife
Volume8
DOIs
StatePublished - Dec 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Jafree, D. J., Moulding, D., Kolatsi-Joannou, M., Tejedor, N. P., Price, K. L., Milmoe, N., Walsh, C., Correra, R. M., Winyard, P. J. D., Harris, P. C., Ruhrberg, C., Walker-Samuel, S., Riley, P. R., Woolf, A. S., Scambler, P. J., & Long, D. A. (2019). Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease. eLife, 8, [e48183]. https://doi.org/10.7554/eLife.48183