Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional programs.
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are interpreted in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs. Unexpectedly, β-catenin and Smad1 binding were associated with both transcriptional activation and repression, with Wnt-repressed genes often lacking canonical Tcf DNA binding motifs, suggesting a novel mode of direct repression. Combinatorial Wnt and BMP signaling was mediated by Smad1 and β-catenin co-occupying hundreds of cis-regulatory DNA elements, and by a crosstalk whereby Wnt negatively regulates BMP ligand expression in the foregut. These results extend our understanding of gastrointestinal organogenesis and of how Wnt and BMP might coordinate genomic responses in other contexts.
['Stevens|Mariana L|ML|', 'Chaturvedi|Praneet|P|', 'Rankin|Scott A|SA|', 'Macdonald|Melissa|M|', 'Jagannathan|Sajjeev|S|', 'Yukawa|Masashi|M|', 'Barski|Artem|A|', 'Zorn|Aaron M|AM|0000-0003-3217-3590']
D000818:Animals D001483:Base Sequence D019521:Body Patterning D019485:Bone Morphogenetic Proteins D002843:Chromatin D004064:Digestive System D018507:Gene Expression Regulation, Developmental D016678:Genome D011485:Protein Binding D051898:Smad1 Protein D014158:Transcription, Genetic D059467:Transcriptome D060449:Wnt Signaling Pathway D014982:Xenopus laevis D051176:beta Catenin
Wnt β-Catenin BMP Smad1 Foregut Hindgut Endoderm Mesoderm Xenopus RNA-seq ChIP-seq