Polycystin Signaling Is Required for Directed Endothelial Cell Migration and Lymphatic Development

Patricia Outeda, David L. Huso, Steven A. Fisher, Marc K. Halushka, Hyunho Kim, Feng Qian, Gregory G. Germino, Terry Watnick

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)634-644
Number of pages11
JournalCell Reports
Volume7
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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