Global inhibition of Lef1/Tcf-dependent Wnt signaling at its nuclear end point abrogates development in transgenic Xenopus embryos.

The Journal of Biological Chemistry
Tom DerooK Vleminckx

Abstract

Analysis of canonical Wnt signaling during vertebrate development by means of knock-out or transgenic approaches is often hampered by functional redundancy as well as pathway bifurcations downstream of the manipulated components. We report the design of an optimized chimera capable of blocking transcriptional activation of Lef1/Tcf-beta-catenin target genes, thus enabling intervention with the canonical Wnt pathway at its nuclear end point. This construct was made hormone-inducible, both functionally and transcriptionally, and was transgenically integrated in Xenopus embryos. Down-regulation of target genes was clearly observed upon treatment of these embryos with dexamethasone. In addition, exposure of variously aged transgenic embryos to dexamethasone caused complex phenotypes with many new but also several recognizable features stemming from inhibition of canonical Wnt signaling. At least in some tissues, a significant reduction in cell proliferation and an increase in programmed cell death appeared to underlie these phenotypes. Our inducible transgenic system can serve a broad range of experimental settings designed to unveil new functional aspects of Lef1/Tcf-beta-catenin signaling during vertebrate embryogenesis.

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Citations

Sep 2, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hong Thi TranKris Vleminckx
Aug 14, 2008·Biology of the Cell·Albert ChesneauOdile J Bronchain
Apr 6, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Kyle E McCoyPeter D Vize
Dec 21, 2016·Development·Melanie RotheSusanne J Kühl
Dec 23, 2008·Mechanisms of Development·Jon P LyonsPierre D McCrea

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