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

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Science  21 Mar 2014:
Vol. 343, Issue 6177, pp. 1353-1356
DOI: 10.1126/science.1248373

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Coordinated Hair Growth

Wnt/β-catenin signaling is a key pathway that plays a conserved role in regulating stem cell function during adult tissue regeneration. Using time-lapse imaging of live mice, Deschene et al. (p. 1353) show that genetic activation of β-catenin within hair follicle stem cells generates axes of hair growth by coordinated cell divisions and cell movements, even when the normal niches—the dermal papillae—are laser-ablated. Activated β-catenin enhances Wnt ligand secretion, and these ligands can then activate Wnt signaling in adjacent cells that do not have activated β-catenin, indicating how activated stem cells could influence neighboring cells during normal growth and in cancer.

Abstract

Wnt/β-catenin signaling is critical for tissue regeneration. However, it is unclear how β-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of β-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. β-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 β-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/β-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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