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Tankyrase is necessary for canonical Wnt signaling during kidney development

Courtney M Karner1, Calli E Merkel, Michael Dodge

  • 1Department of Internal Medicine (Nephrology) and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|June 16, 2010
PubMed

Insights

Poly(ADP-ribose) polymerases (PARPs) Tankyrase 1 and 2 are crucial for mouse development, particularly in kidney and lung tissues. Their inhibition affects Wnt signaling, suggesting tankyrases are core pathway components.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Signaling

Background:

  • Tankyrase 1 and 2 (Tnks1 and 2) are poly(ADP-ribose) polymerases (PARPs) implicated in Wnt signaling.
  • Previous studies suggested limited roles in certain contexts, with no observed activity during zebrafish embryogenesis.
  • This raised questions about their general importance in the Wnt pathway.

Purpose of the Study:

  • To investigate the role of Tankyrase 1 and 2 in mammalian development.
  • To determine if tankyrases are core components of the canonical Wnt signaling pathway.
  • To assess the therapeutic potential of tankyrase inhibitors.

Main Methods:

  • Examined expression patterns of Tnks1 and 2 during mouse development.
  • Utilized tankyrase inhibitors to block activity in developing mouse kidneys and lungs.
  • Assessed rescue effects by activating beta-catenin.
  • Evaluated reversibility of tankyrase inhibitor treatment in cell cultures.

Main Results:

  • Tnks1 and 2 are broadly expressed during mouse development and essential for kidney and lung formation.
  • Inhibition of tankyrase activity in kidneys mimicked the effects of blocking Wnt ligand production.
  • The Wnt pathway specificity was confirmed by rescue experiments with beta-catenin activation.
  • Tankyrase inhibition was found to be reversible in certain cell types.

Conclusions:

  • Tankyrases are essential regulators of kidney and lung development in mice.
  • These findings establish tankyrases as core components of the canonical Wnt signaling pathway.
  • Tankyrase inhibitors show promise for broad application as Wnt signaling antagonists.

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