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.

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

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Item Type:	Article
Title:	Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling
Creators Name:	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. and Mosimann, C.
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.
Keywords:	CRISPR-Cas9, Cardiovascular Development, Congenital Heart Disease, Heart, Transcription, Wnt Signaling, Animals, Mice, Zebrafish
Source:	Genes & Development
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Volume:	32
Number:	21-22
Page Range:	1443-1458
Date:	1 November 2018
Additional Information:	Copyright © 2018, Cantù et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons Attribution-NonCommercial 4.0 International licence.
Official Publication:	https://doi.org/10.1101/gad.315531.118
PubMed:	View item in PubMed

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