4.8 Article

β-Catenin Activation Regulates Tissue Growth Non-Cell Autonomously in the Hair Stem Cell Niche

Journal

SCIENCE
Volume 343, Issue 6177, Pages 1353-1356

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1248373

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Funding

  1. American Cancer Society [RSG-12-059-02]
  2. Yale Spore Grant National Cancer Institute, NIH [2P50CA121974]
  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [1R01AR063663-01]
  4. Yale Stem Cell Center Lo Fellowship
  5. NIH Predoctoral Program in Cellular and Molecular Biology [TG32 GM007223]
  6. CT Innovations [13-SCA-YALE-20]
  7. Rheumatic Diseases Research Core Centers [5 P30 AR053495-07]

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Wnt/beta-catenin signaling is critical for tissue regeneration. However, it is unclear how beta-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of beta-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. beta-Catenin activation is sufficient to induce hair growth independently of mesenchymal dermal papilla niche signals normally required for hair regeneration. Wild-type cells are co-opted into new hair growths by beta-catenin mutant cells, which non-cell autonomously activate Wnt signaling within the neighboring wild-type cells via Wnt ligands. This study demonstrates a mechanism by which Wnt/beta-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.

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