期刊
DEVELOPMENTAL DYNAMICS
卷 239, 期 7, 页码 2014-2023出版社
WILEY
DOI: 10.1002/dvdy.22340
关键词
Wnt; beta-catenin; tankyrase; porcupine; metanephros; kidney; development; ureteric bud; renal vesicle
资金
- American Heart Association [0730236N]
- NIH [R01DK080004, R01GM076398]
- Susan Irene Simons Kidney Cancer Foundation [R01GM079554]
- NIGMS [R01GM079554]
- Welch Foundation [Welch I-1596]
- American Heart Association
- NIH
- Susan Irene Simons Kidney Cancer Foundation
- NIGMS
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. Developmental Dynamics 239:2014-2023, 2010. (C) 2010 Wiley-Liss, Inc.
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