Abstract
Wnt/β‐catenin signaling is an important cell‐to‐cell signaling mechanism that controls gene expression during embryonic development and is critically implicated in human diseases. Developmental, cellular, and transcriptional responses to Wnt signaling are remarkably context‐specific in different biological processes. While nuclear localization of β‐catenin is the key to activation of the Wnt/β‐catenin pathway and target gene expression, the molecular mechanisms of how the same Wnt/β‐catenin signaling pathway induces specific responses remain undetermined. Recent advances in high‐throughput sequencing technologies and the availability of genome information for Xenopus tropicalis have enabled us to uncover a genome‐wide view of Wnt/β‐catenin signaling in early vertebrate embryos, which challenges previous concepts about molecular mechanisms of Wnt target gene regulation. In this review, we summarize our experimental approaches, introduce the technologies we employed and focus on recent findings about Wnt target gene regulation from Xenopus research. We will also discuss potential functions of widespread β‐catenin binding in the genome that we discovered in this species.
Highlights
The Wnt/b-catenin pathway is an important cell-to-cell signaling mechanism conserved among animals including humans (Loh, van Amerongen, & Nusse, 2016)
The unique experimental accessibility and size of the Xenopus embryo has made it the model system of choice to apply recent advances in research technologies, such as high-throughput sequencing in order to gain a genomewide view of target gene regulation by Wnt/b-catenin signaling in early embryogenesis
Conventional research on Wnt signaling has logically focused on identifying mechanisms that are universally used in different contexts
Summary
The Wnt/b-catenin pathway is an important cell-to-cell signaling mechanism conserved among animals including humans (Loh, van Amerongen, & Nusse, 2016). 1997; Schneider, Steinbeisser, Warga, & Hausen, 1996; Schohl & Fagotto, 2002) This maternal b-catenin sets up poised transcription of direct dorsal-specific maternal Wnt target genes (Brannon, Gomperts, Sumoy, Moon, & Kimelman, 1997; Laurent, Blitz, Hashimoto, Rothbacher, & Cho, 1997; McKendry, Hsu, Harland, & Grosschedl, 1997), which proceed with full transcription after the MBT (Blythe, Cha, Tadjuidje, Heasman, & Klein, 2010). The expression of these maternal Wnt target genes in dorsal blastomeres is responsible for establishing subsequent dorsal development (Figure 3). While b-catenin association to Wnt target gene sequences is required, context-specific mechanisms are required for Wnt target gene transcription
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