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

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 verte...

Descripción completa

Detalles Bibliográficos
Autores principales: Cantù, Claudio, Felker, Anastasia, Zimmerli, Dario, Prummel, Karin D., Cabello, Elena M., Chiavacci, Elena, Méndez-Acevedo, Kevin M., Kirchgeorg, Lucia, Burger, Sibylle, Ripoll, Jorge, Valenta, Tomas, Hausmann, George, Vilain, Nathalie, Aguet, Michel, Burger, Alexa, Panáková, Daniela, Basler, Konrad, Mosimann, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217730/
https://www.ncbi.nlm.nih.gov/pubmed/30366904
http://dx.doi.org/10.1101/gad.315531.118
Descripción
Sumario: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.

Ejemplares similares