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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental
  • Genetic Heterogeneity
  • Humans
  • Kidney / embryology
  • Kidney / metabolism*
  • Kinetics
  • Lymphangiogenesis / genetics*
  • Lymphatic Vessels / embryology
  • Lymphatic Vessels / metabolism*
  • Mammals / embryology
  • Mammals / genetics
  • Mammals / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Polycystic Kidney Diseases / embryology
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / metabolism
  • Spatio-Temporal Analysis
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Vascular Endothelial Growth Factor C