Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development

Boni A. 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 journalArticlepeer-review

13 Citations (Scopus)
7 Downloads (Pure)


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
Issue number7
Early online date25 Jun 2020
Publication statusPublished - 24 Jul 2020

Bibliographical note

We thank Jessica Cheung (UC Irvine) and Yvonne Turnbull (University of
Aberdeen) for technical and management support; Gert Jan Veenstra (Radboud University, Nijmegen) for discussion; and Adam Lynch and Victor Velecela (University of Aberdeen), for comments on the manuscript. We also thank Professor Masanori Taira (University of Tokyo, currently Chuo University) and Dr Norihiro Sudou (Nara Institute of Science and Technology, currently Tokyo Women's Medical University) for the siamois antibody; and Professor Dan Kessler (University of Pennsylvania) for siamois constructs. This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) in the United Kingdom (BB/M001695/1) and by NIH in the United States (NIH GM126395). SH additionally acknowledges personal funding support as a Royal Society/Leverhulme Trust Senior Research Fellow (SRF\R1\191017).


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


Dive into the research topics of 'Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development'. Together they form a unique fingerprint.

Cite this