naked cuticle targets dishevelled to antagonize Wnt signal transduction
- Raphaël Rousset1,2,7,
- Judith A. Mack1,2,5,7,
- Keith A. Wharton, Jr.1,2,3,6,
- Jeffrey D. Axelrod3,
- Ken M. Cadigan1,4,
- Matthew P. Fish1,2,
- Roel Nusse1, and
- Matthew P. Scott1,2,8
- Departments of 1Developmental Biology, 2Genetics, and 3Pathology, Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine, Stanford, California 94305, USA; 4Department of Biology, Kraus Natural Science Building, University of Michigan, Ann Arbor, Michigan 48109, USA
Abstract
In Drosophila embryos the protein Naked cuticle (Nkd) limits the effects of the Wnt signal Wingless (Wg) during early segmentation.nkd loss of function results in segment polarity defects and embryonic death, but how nkd affects Wnt signaling is unknown. Using ectopic expression, we find that Nkd affects, in a cell-autonomous manner, a transduction step between the Wnt signaling components Dishevelled (Dsh) and Zeste-white 3 kinase (Zw3). Zw3 is essential for repressing Wg target-gene transcription in the absence of a Wg signal, and the role of Wg is to relieve this inhibition. Our double-mutant analysis shows that, in contrast to Zw3, Nkd acts when the Wg pathway is active to restrain signal transduction. Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh. Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity. Our results suggest that Nkd acts directly through Dsh to limit Wg activity and thus determines how efficiently Wnt signals stabilize Armadillo (Arm)/β-catenin and activate downstream genes.
Keywords
Footnotes
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Present addresses: 5Cleveland Clinic Florida, Research Laboratory, Building 2950, 3000 West Cypress Creek Road, Ft. Lauderdale, FL 33309, USA; 6Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center NB6.440, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
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↵7 These authors contributed equally to the work.
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↵8 Corresponding author.
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E-MAIL scott{at}cmgm.stanford.edu; FAX (650) 725-7739.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.869201.
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- Received November 27, 2000.
- Accepted January 22, 2001.
- Cold Spring Harbor Laboratory Press
