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Essential long-range action of Wingless/Wnt in adult intestinal compartmentalization.

Ai Tian | Deepesh Duwadi | Hassina Benchabane | Yashi Ahmed
PLoS genetics | 2019

Signal transduction activated by Wingless/Wnt ligands directs cell proliferation and fate specification in metazoans, and its overactivation underlies the development of the vast majority of colorectal cancers. In the conventional model, the secretion and movement of Wingless to cells distant from its source of synthesis are essential for long-range signaling in tissue patterning. However, this model was upended recently by an unanticipated finding: replacement of wild-type Drosophila Wingless with a membrane-tethered form produced viable adults with largely normal external morphology, which suggested that Wingless secretion and movement are dispensable for tissue patterning. Herein, we tested this foundational principle in the adult intestine, where Wingless signaling gradients coincide with all major boundaries between compartments. We find that the critical roles of Wingless during adult intestinal development, which include regulation of target gene activation, boundary formation, stem cell proliferation, epithelial cell fate specification, muscle differentiation, gut folding, and signaling crosstalk with the Decapentaplegic pathway, are all disrupted by Wingless tethering. These findings provide new evidence that supports the requirement for the direct, long-range action of Wingless in tissue patterning, with relevance for animal development, tissue homeostasis and Wnt-driven disease.

Pubmed ID: 31194729

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM122222
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM113132
  • Agency: NIH HHS, United States
    Id: P40 OD018537
  • Agency: NCI NIH HHS, United States
    Id: P30 CA023108
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM121421
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084947

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PRISM (tool)

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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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