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XB-ART-7249
Dev Cell April 1, 2002; 2 (4): 449-61.

Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.

Cheyette BN , Waxman JS , Miller JR , Takemaru K , Sheldahl LC , Khlebtsova N , Fox EP , Earnest T , Moon RT .


Abstract
Dapper was isolated in a screen for proteins interacting with Dishevelled, a key factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper increases Axin and GSK-3 in this complex, resulting in decreased soluble beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA from Xenopus embryos results in loss of notochord and head structures, demonstrating that Dapper is required for normal vertebrate development.

PubMed ID: 11970895
Article link: Dev Cell
Grant support: [+]
Genes referenced: csnk1g2 dact1 dvl2 hhat jun mapk8 ppp1r9b
Morpholinos: dact1 MO1


Article Images: [+] show captions


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