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?-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

ABSTRACT: Wnt/?-catenin signaling is critical for tissue regeneration. However, it is unclear how ?-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of ?-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. ?-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 ?-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/?-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.

SUBMITTER: Deschene ER

PROVIDER: S-EPMC4096864 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

Deschene Elizabeth R ER Myung Peggy P Rompolas Panteleimon P Zito Giovanni G Sun Thomas Yang TY Taketo Makoto M MM Saotome Ichiko I Greco Valentina V

Science (New York, N.Y.) 20140301 6177

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 regene ...[more]

PMID: 24653033

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Project description:In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge are regulated by the surrounding microenvironment, or niche. The activation of such stem cells is cyclic, involving periodic beta-catenin activity. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin.

Dataset Information

?-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

Publications

β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

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