Abstract
SummaryAlthough 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 feedforward 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.
Highlights
The maternal-to-zygotic transition activates transcription of gene batteries under the control of transcription factors and signaling pathway components that are deposited in the egg by the maternal genome
We combine transcriptomics using RNA sequencing (RNA-seq) with genome-wide b-catenin association using ChIP-seq to identify stage-specific direct Wnt target genes
We propose coherent feedforward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of b-catenin association
Summary
The maternal-to-zygotic transition activates transcription of gene batteries under the control of transcription factors and signaling pathway components that are deposited in the egg by the maternal genome. Maternal Wnt signaling-regulated b-catenin protein controls subsequent expression of direct target genes (Blythe et al, 2010), including siamois (Brannon et al, 1997; Laurent et al, 1997) and nodal (McKendry et al, 1997; Smith et al, 1995), by the midblastula stage These genes are among the earliest zygotically expressed factors (Collart et al, 2014; Gentsch et al, 2019a, 2019b; Owens et al, 2016; Skirkanich et al, 2011; Tan et al, 2013; Yang et al, 2002) and function to establish dorsal embryonic cell fates (e.g., Ding et al, 2017; Kessler, 1997; Smith et al, 1995) together with subsequently expressed dorsal genes, such as goosecoid (gsc) and noggin (nog) (Ding et al, 2017; Wessely et al, 2001).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
