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


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 (2018). Mutations in and genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling. Genes and Development, 32(21-22):1443-1458.

Abstract

Bcl9 and Pygopus (Pygo) are obligate Wnt/β-catenin cofactors in , 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 and in human congenital heart defects.

Abstract

Bcl9 and Pygopus (Pygo) are obligate Wnt/β-catenin cofactors in , 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 and in human congenital heart defects.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 November 2018
Deposited On:15 Feb 2019 16:27
Last Modified:25 Sep 2019 00:08
Publisher:Cold Spring Harbor Laboratory Press
ISSN:0890-9369
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/gad.315531.118
PubMed ID:30366904

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