BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian Skin


Epidermis, a thin layer of stratified epithelium forming the outmost surface of the skin, provides the crucial function to protect animals from environmental insults, such as bacterial pathogens and water loss. This barrier function is established in embryogenesis, during which single layered epithelial cells differentiate into distinct layers of keratinocytes. Many human genetic diseases are featured with epidermal disruption, affecting at least one in five patients. Skin regeneration and future therapeutics require a thorough understanding of the molecular mechanisms underlying epidermal stratification. Wnt ligands have been implicated in hair follicle induction during skin development and self-renewal of stem cells in the interfollicular epidermis of adult skin; however, little is known about the mechanism of how Wnt signaling controls epidermal stratification during embryogenesis. In this study, by using a genetic mouse model to disrupt Wnt production in skin development, we found that signaling of epidermal Wnt in the dermis initiate mesenchymal responses by activating a Bone Morphogenetic Protein (BMP) and Fibroblast growth factor (FGF) signaling cascade, and this activation is required for feedback regulations in the embryonic epidermis to control stratification. Our findings identify a genetic hierarchy of signaling essential for epidermal-mesenchymal interactions, and promote our understanding of mammalian skin development.


Vyšlo v časopise: BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian Skin. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004687
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004687

Souhrn

Epidermis, a thin layer of stratified epithelium forming the outmost surface of the skin, provides the crucial function to protect animals from environmental insults, such as bacterial pathogens and water loss. This barrier function is established in embryogenesis, during which single layered epithelial cells differentiate into distinct layers of keratinocytes. Many human genetic diseases are featured with epidermal disruption, affecting at least one in five patients. Skin regeneration and future therapeutics require a thorough understanding of the molecular mechanisms underlying epidermal stratification. Wnt ligands have been implicated in hair follicle induction during skin development and self-renewal of stem cells in the interfollicular epidermis of adult skin; however, little is known about the mechanism of how Wnt signaling controls epidermal stratification during embryogenesis. In this study, by using a genetic mouse model to disrupt Wnt production in skin development, we found that signaling of epidermal Wnt in the dermis initiate mesenchymal responses by activating a Bone Morphogenetic Protein (BMP) and Fibroblast growth factor (FGF) signaling cascade, and this activation is required for feedback regulations in the embryonic epidermis to control stratification. Our findings identify a genetic hierarchy of signaling essential for epidermal-mesenchymal interactions, and promote our understanding of mammalian skin development.


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Genetika Reprodukčná medicína

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