Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling
Authors
- 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
Journal
- Genes & Development
Citation
- Genes Dev 32 (21-22): 1443-1458
Abstract
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.