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

authors

  • CANTU, CLAUDIO
  • FELKER, ANASTASIA
  • ZIMMERLI, DARIO
  • PRUMMEL, KARIN D.
  • CABELLO, ELENA M.
  • CHIAVACCI, ELENA
  • MENDEZ ACEVEDO, KEVIN M.
  • KIRCHGEORG, LUCIA
  • BURGER, SIBYLLE
  • RIPOLL LORENZO, JORGE
  • VALENTA, TOMAS
  • HAUSMANN, GEORGE
  • VILAIN, NATHALIE
  • AGUET, MICHEL
  • BURGER, ALEXA
  • PANAKOVA, DANIELA
  • BASLER, KONRAD
  • MOSIMANN, CHRISTIAN

publication date

  • November 2018

start page

  • 1443

end page

  • 1458

issue

  • 21-22

volume

  • 32

international standard serial number (ISSN)

  • 0890-9369

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.

keywords

  • crispr-cas9; cardiovascular development; congenital heart disease; heart; transcription; wnt signaling; cardiac neural crest; chromosome 1q21.1; valve development; transcription; legless; rearrangements; proliferation; mutagenesis; recruitment; deficient