Smad7-Induced β-Catenin Degradation Alters Epidermal Appendage Development

To assess whether Smad signaling affects skin development, we generated transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes, including epidermal stem cells. Smad7 transgene induction perturbed hair follicle morphogenesis and differentiation, but accelerated sebaceous glan...

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Bibliographic Details
Published in:Developmental cell 2006-09, Vol.11 (3), p.301-312
Main Authors: Han, Gangwen, Li, Allen G., Liang, Yao-Yun, Owens, Philip, He, Wei, Lu, Shilong, Yoshimatsu, Yasuhiro, Wang, Donna, ten Dijke, Peter, Lin, Xia, Wang, Xiao-Jing
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Biological and medical sciences
Cell Differentiation
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Cell Proliferation
DEVBIO
Down-Regulation
Epidermis - metabolism
Epidermis - pathology
Fundamental and applied biological sciences. Psychology
Hair Follicle - metabolism
Hair Follicle - physiology
Humans
HUMDISEASE
Keratinocytes - metabolism
Mice
Mice, Transgenic
Molecular and cellular biology
Morphogenesis
Sebaceous Glands - physiology
Signal Transduction
SIGNALING
Smad7 Protein - metabolism
Smad7 Protein - physiology
Stem Cells - physiology
Ubiquitin-Protein Ligases - metabolism
Wnt Proteins - metabolism
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Summary:To assess whether Smad signaling affects skin development, we generated transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes, including epidermal stem cells. Smad7 transgene induction perturbed hair follicle morphogenesis and differentiation, but accelerated sebaceous gland morphogenesis. Further analysis revealed that independent of its role in anti-Smad signaling, Smad7 bound β-catenin and induced β-catenin degradation by recruiting an E3 ligase, Smurf2, to the Smad7/β-catenin complex. Consequently, Wnt/β-catenin signaling was suppressed in Smad7 transgenic hair follicles. Coexpression of the Smurf2 and Smad7 transgenes exacerbated Smad7-induced abnormalities in hair follicles and sebaceous glands. Conversely, when endogenous Smad7 was knocked down, keratinocytes exhibited increased β-catenin protein and enhanced Wnt signaling. Our data reveal a mechanism for Smad7 in antagonizing Wnt/β-catenin signaling, thereby shifting the skin differentiation program from forming hair follicles to sebaceous glands.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2006.06.014