Foxh1/Nodal defines context-specific direct maternal Wnt/β-catenin target gene regulation in early development

Boni Afouda, Yukio Nakamura, Sophie Shaw, Rebekah M Charney, Kitt D. Paraiso, Ira L. Blitz, Ken W.Y. Cho, Stefan Hoppler* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

While Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target gene
expression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target gene
regulation. We combine transcriptomics using RNA-seq with genome-wide β--catenin association using ChIP-seq to identify stage-specific direct Wnt
target genes. We propose coherent feed forward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin-association overlaps with Foxh1-associated regulatory sequences, and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease.
Original languageEnglish
Article number101314
Number of pages34
JournaliScience
Volume23
Issue number7
Early online date25 Jun 2020
DOIs
Publication statusPublished - 24 Jul 2020

Keywords

  • Ctnnb1
  • β-catenin
  • Wnt signaling
  • Zygotic Gene Activation
  • Mid-Blastula Transition
  • Axis induction
  • Biological Sciences
  • Molecular Biology
  • Developmental Biology

ASJC Scopus subject areas

  • General

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