Cantu, ClaudioFelker, AnastasiaZimmerli, DarioPrummel, Karin D.Cabello, Elena M.Chiavacci, ElenaMendez-Acevedo, Kevin M.Kirchgeorg, LuciaBurger, SibylleRipoll, JorgeValenta, TomasHausmann, GeorgeVilain, NathalieAguet, MichelBurger, AlexaPanakova, DanielaBasler, KonradMosimann, Christian2018-12-132018-12-132018-12-132018-11-0110.1101/gad.315531.118https://infoscience.epfl.ch/handle/20.500.14299/152721WOS:000451237000008Bcl9 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.Cell BiologyDevelopmental BiologyGenetics & Hereditycrispr-cas9cardiovascular developmentcongenital heart diseasehearttranscriptionwnt signalingcardiac neural crestchromosome 1q21.1valve developmentleglessrearrangementsproliferationmutagenesisrecruitmentdeficientMutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/beta-catenin signalingtext::journal::journal article::research article