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

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

Author information

  • 1Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • 2Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 3Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • 4Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 5National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 6Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: twatnick@medicine.umaryland.edu.

Abstract

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.

PMID:
24767998
PMCID:
PMC4040350
DOI:
10.1016/j.celrep.2014.03.064
[PubMed - indexed for MEDLINE]
Free PMC Article

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