Polycystin signaling is required for directed endothelial cell migration and lymphatic development

Cell Rep. 2014 May 8;7(3):634-44. doi: 10.1016/j.celrep.2014.03.064. Epub 2014 Apr 24.


Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1) and PKD2 (polycystin-2). Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Polarity
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lymph Nodes / embryology*
  • Lymph Nodes / metabolism
  • Lymphatic Vessels / embryology
  • Lymphatic Vessels / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Polycystic Kidney, Autosomal Dominant / pathology
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction*
  • TRPP Cation Channels / antagonists & inhibitors
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism*


  • RNA, Small Interfering
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein