title: Tankyrase is necessary for canonical Wnt signaling during kidney development.
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 beta-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.
authors.affiliation: Department of Internal Medicine (Nephrology) and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Karner
authors.forename: Calli E
authors.initials: CE
authors.lastname: Merkel
authors.forename: Michael
authors.initials: M
authors.lastname: Dodge
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.forename: Jianming
authors.initials: J
authors.lastname: Lu
authors.forename: Chuo
authors.initials: C
authors.lastname: Chen
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lum
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carroll
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology*; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D038501:Tankyrases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D051153:Wnt Proteins; D051176:beta Catenin; D038501:Tankyrases; D018021:Lithium Chloride