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

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.


Published in:
Genes & Development, 32, 21-22, 1443-1458
Year:
Nov 01 2018
Publisher:
Cold Spring Harbor, COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
ISSN:
0890-9369
1549-5477
Keywords:
Note:
This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Laboratories:


Note: The status of this file is: Anyone


 Record created 2018-12-13, last modified 2020-05-31

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