Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling


  • C. Cantù
  • A. Felker
  • D. Zimmerli
  • K.D. Prummel
  • E.M. Cabello
  • E. Chiavacci
  • K.M. Méndez-Acevedo
  • L. Kirchgeorg
  • S. Burger
  • J. Ripoll
  • T. Valenta
  • G. Hausmann
  • N. Vilain
  • M. Aguet
  • A. Burger
  • D. Panáková
  • K. Basler
  • C. Mosimann


  • Genes & Development


  • Genes Dev 32 (21-22): 1443-1458


  • Bcl9 and Pygopus (Pygo) are obligate Wnt/β-catenin cofactors in Drosophila, 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 BCL9 and BCL9L in human congenital heart defects.