XB-ART-7249Dev Cell April 1, 2002; 2 (4): 449-61.
Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.
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
Genes referenced: csnk1g2 dact1 dvl2 hhat jun mapk8 ppp1r9b
Morpholinos: dact1 MO1
Article Images: [+] show captions
|Figure 7. Dpr Expression(A–G) mRNA whole-mount in situ hybridizations.(A) Sense controls: gastrula (bottom) and tailbud (top).(B) Early gastrula (stage 10 vegetal view; top, dorsal; dl, dorsal lip).(C) Early neurula (stage 14 dorsal view; top, anterior; ant ne, anterior neurectoderm).(D) Early tailbud (stage 19 dorsal view; top, anterior).(E and F) Tailbud (stage 21; [E], anterior view; [F], lateral view; arrows, neural folds; ey, eye fields; tb, tailbud).(G) Tadpole (stage 41 lateral view; left, anterior).(H) Northern analysis adult MDpr1 expression: br, brain; hrt, heart; kd, kidney; lvr, liver; lng, lung; ml, muscle; skn, skin; si, small intestine; spn, spleen; stm, stomach; ts, testis; thy, thymus.|