Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling.
Genes Dev. 2018 Oct 26;:
Authors: Cantù C, Felker A, Zimmerli D, Prummel KD, Cabello EM, Chiavacci E, Méndez-Acevedo KM, Kirchgeorg L, Burger S, Ripoll J, Valenta T, Hausmann G, Vilain N, Aguet M, Burger A, Panáková D, Basler K, Mosimann C
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.
PMID: 30366904 [PubMed – as supplied by publisher]