Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.
Electrochemical Signaling in Development and Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin-Buch, Germany.
Genes Dev. 2018 Nov 1;32(21-22):1443-1458. doi: 10.1101/gad.315531.118. Epub 2018 Oct 26.
Bcl9 and Pygopus (Pygo) are obligate Wnt/β-catenin cofactors in , yet their contribution to Wnt signaling during vertebrate development remains unresolved. Combining zebrafish and mouse genetics, we document a conserved, β-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development. Disrupting the β-catenin-BCL9-Pygo complex results in a broadly maintained canonical Wnt response yet perturbs heart development and proper expression of key cardiac regulators. Our work highlights BCL9 and Pygo as selective β-catenin cofactors in a subset of canonical Wnt responses during vertebrate development. Moreover, our results implicate alterations in and in human congenital heart defects.
Bcl9 和 Pygopus（Pygo）是 Wnt/β-连环蛋白在 中的必需辅因子，但它们在脊椎动物发育过程中对 Wnt 信号的贡献仍未得到解决。通过结合斑马鱼和小鼠遗传学，我们记录了 BCL9 和 Pygo 蛋白在脊椎动物心脏发育过程中保守的、与 β-连环蛋白相关的功能。破坏 β-连环蛋白-BCL9-Pygo 复合物会导致广泛维持的经典 Wnt 反应，但会扰乱心脏发育和关键心脏调节因子的正确表达。我们的工作强调了 BCL9 和 Pygo 作为经典 Wnt 反应中一组选择性 β-连环蛋白辅因子在脊椎动物发育过程中的作用。此外，我们的结果表明人类先天性心脏缺陷中 和 的改变。
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