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Overview
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Background
Windorphen is a Wnt inhibitor that selectively abrogates the Wnt signaling for ventral development. Wnt protein is a family of signaling proteins that interacts on the Wnt/β-Catenin pathways during embryotic development, cell proliferation, migration and adult tissue homeostasis. In canonical Wnt/β-catenin reporter cell line STF293, Windorphen dose-dependently inhibits Wnt3a-inducible TOPFLASH-luciferase activity (IC50 of 1.5 mM). In human colon adenocarcinomaSW480 cells with defective APC gene that constitutively activates Wnt signaling, 72 h treatment of Windorphen causes a wide spread apoptosis. [1] In zebrafish embryos, Windorphen leads to apparent expansion of the dorsal markers (pax2.1) and marker of rhombomeres 3 and 5 at the six-somite stage (krox0). Windorphen selectively inhibits Wnt signaling in ventral and lateral regions of the 50% epiboly stage embryo (5.3 hpf). In addition, Windoprhen treatment rescues the telencephalon/eye phenotype in the mbl mutant zebrafish (i.e. a defective Axin1/β-catenin destruction complex causes abnormal activation of Wnt signaling and the loss of telencephalon and eyes.) [1]
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