Abstract
Epidermal stratification of the mammalian skin requires proliferative basal progenitors to generate intermediate cells that separate from the basal layer and are replaced by post-mitotic cells. Although Wnt signaling has been implicated in this developmental process, the mechanism underlying Wnt-mediated regulation of basal progenitors remains elusive. Here we show that Wnt secreted from proliferative basal cells is not required for their differentiation. However, epidermal production of Wnts is essential for the formation of the spinous layer through modulation of a BMP-FGF signaling cascade in the dermis. The spinous layer defects caused by disruption of Wnt secretion can be restored by transgenically expressed Bmp4. Non-cell autonomous BMP4 promotes activation of FGF7 and FGF10 signaling, leading to an increase in proliferative basal cell population. Our findings identify an essential BMP-FGF signaling axis in the dermis that responds to the epidermal Wnts and feedbacks to regulate basal progenitors during epidermal stratification.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Morphogenetic Protein 4 / genetics
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism*
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Cell Proliferation
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Epidermal Cells*
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Epidermis / embryology
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Epidermis / growth & development
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Epidermis / metabolism
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Fibroblast Growth Factor 10 / genetics
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Fibroblast Growth Factor 10 / metabolism
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Fibroblast Growth Factor 7 / genetics
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Fibroblast Growth Factor 7 / metabolism
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Fibroblast Growth Factors / genetics
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Fibroblast Growth Factors / metabolism*
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Gene Expression Regulation, Developmental
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Mice, Transgenic
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction
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Skin / cytology
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Skin / embryology
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Skin / growth & development
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Skin / metabolism*
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Smad1 Protein / metabolism
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Smad5 Protein / metabolism
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Smad8 Protein / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Wnt Signaling Pathway* / genetics
Substances
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Fgf10 protein, mouse
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Fgf7 protein, mouse
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Fibroblast Growth Factor 10
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Gpr177 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Receptors, G-Protein-Coupled
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Smad1 Protein
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Smad1 protein, mouse
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Smad5 Protein
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Smad5 protein, mouse
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Smad8 Protein
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Smad9 protein, mouse
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Trans-Activators
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Trp63 protein, mouse
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Fibroblast Growth Factor 7
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Fibroblast Growth Factors