ZFIN ID: ZDB-PUB-181028-1
Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling.
Cantù, C., Felker, A., Zimmerli, D., Prummel, K.D., Cabello, E.M., Chiavacci, E., Méndez-Acevedo, K.M., Kirchgeorg, L., Burger, S., Ripoll, J., Valenta, T., Hausmann, G., Vilain, N., Aguet, M., Burger, A., Panáková, D., Basler, K., Mosimann, C.
Date: 2018
Source: Genes & Development   32(21-22): 1443-1458 (Journal)
Registered Authors: Burger, Alexa, Burger, Sibylle, Chiavacci, Elena, Felker, Anastasia, Mosimann, Christian, Panáková, Daniela, Prummel, Karin
Keywords: CRISPR–Cas9, Wnt signaling, cardiovascular development, congenital heart disease, heart, transcription
MeSH Terms:
  • Animals
  • Heart/embryology
  • Heart Defects, Congenital/genetics*
  • Intracellular Signaling Peptides and Proteins/genetics*
  • Mice
  • Mutation
  • Myocardium/metabolism
  • Transcription Factors/genetics*
  • Wnt Signaling Pathway*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
  • beta Catenin/metabolism
PubMed: 30366904 Full text @ Genes & Dev.
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.