Publication: Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/beta-catenin signaling
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2018
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Cold Spring Harbor Laboratory Press
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Abstract
Bcl9 and Pygopus (Pygo) are obligate Wnt/beta-catenin cofactors in Drosophila, yet their contribution to Wnt signaling during vertebrate development remains unresolved. Combining zebrafish and mouse genetics, we document a conserved, beta-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development. Disrupting the beta-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 beta-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.
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CRISPR–Cas9, Cardiovascular development, Congenital heart disease, Heart, Transcription, Wnt signaling
Bibliographic citation
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. (2018). Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling.Genes & Development 32(21-22), pp. 1443-1458.