Tankyrase is necessary for canonical Wnt signaling during kidney development

Courtney M. Karner, Calli E. Merkel, Michael Dodge, Zhiqiang Ma, Jianming Lu, Chuo Chen, Lawrence Lum, Thomas J. Carroll

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Recent studies using small molecule antagonists have revealed that the poly(ADP-ribose) polymerases (PARPs) Tankyrase 1 and 2 are critical regulators of canonical Wnt signaling in some cellular contexts. However, the absence of any activity during zebrafish embryogenesis suggested that the tankyrases may not be general/core components of the Wnt pathway. Here, we show that Tnks1 and 2 are broadly expressed during mouse development and are essential during kidney and lung development. In the kidney, blockage of tankyrase activity phenocopies the effect of blocking production of all Wnt ligands. Tankyrase inhibition can be rescued by activation of β-catenin demonstrating its specificity for the Wnt pathway. In addition, treatment with tankyrase inhibitors appears to be completely reversible in some cell types. These studies suggest that the tankyrases are core components of the canonical Wnt pathway and their inhibitors should enjoy broad usage as antagonists of Wnt signaling.

Original languageEnglish (US)
Pages (from-to)2014-2023
Number of pages10
JournalDevelopmental Dynamics
Volume239
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • Development
  • Kidney
  • Metanephros
  • Porcupine
  • Renal vesicle
  • Tankyrase
  • Ureteric bud
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Developmental Biology

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