Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
- Owen J. Sansom1,
- Karen R. Reed1,
- Anthony J. Hayes1,
- Heather Ireland2,
- Hannah Brinkmann1,
- Ian P. Newton3,
- Eduard Batlle4,
- Patricia Simon-Assmann5,
- Hans Clevers4,
- Inke S. Nathke3,
- Alan R. Clarke1,6, and
- Douglas J. Winton2
- 1School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales; 2Cancer Research UK Department of Oncology, Cambridge CB2 2XY, UK; 3School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland; 4Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands; 5INSERM U381, Strasbourg, France.
Abstract
Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of β-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a “crypt progenitor-like” phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.287404.
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↵6 Corresponding author. E-MAIL clarkear{at}cf.ac.uk; FAX 44-0-2920-874116.
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- Accepted April 19, 2004.
- Received October 3, 2003.
- Cold Spring Harbor Laboratory Press
