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GENES & DEVELOPMENT 18:1385-1390, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

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

1 School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales; 2 Cancer Research UK Department of Oncology, Cambridge CB2 2XY, UK; 3 School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland; 4 Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands; 5 INSERM U381, Strasbourg, France.

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 {beta}-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.

[Keywords: Apc; Wnt signaling; intestine; conditional; apoptosis]

Received October 3, 2003; revised version accepted April 19, 2004.


Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.287404.

6 Corresponding author. E-MAIL clarkear{at}cf.ac.uk; FAX 44-0-2920-874116.


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