Wnt/Wingless directs many cell fates during development. Wnt/Wingless signa
ling increases the amount of beta-catenin/Armadillo, which in turn activate
s gene transcription. Here the Drosophila protein D-Axin was shown to inter
act with Armadillo and D-APC. Mutation of d-axin resulted in the accumulati
on of cytoplasmic Armadillo and one of the Wingless target gene products, D
istal-less. Ectopic expression of d-axin inhibited Wingless signaling. Henc
e, D-Axin negatively regulates Wingless signaling by down-regulating the Le
vel of Armadillo. These results establish the importance of the Axin family
of proteins in Wnt/Wingless signaling in Drosophila.