期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms15397
关键词
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资金
- NIH [R37AR047709, RO1DE024570, R56DE023100]
- Penn Skin Biology and Diseases Resource-based Center [P30AR069589]
- Penn Skin Disease Research Center [P30AR057217]
- Monell Phenotyping Core [P30DC011735]
- Dermatology Foundation
Human WNT10A mutations are associated with developmental tooth abnormalities and adolescent onset of a broad range of ectodermal defects. Here we show that beta-catenin pathway activity and adult epithelial progenitor proliferation are reduced in the absence of WNT10A, and identify Wnt-active self-renewing stem cells in affected tissues including hair follicles, sebaceous glands, taste buds, nails and sweat ducts. Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4. We find that beta-catenin interacts directly with region-specific LEF/TCF factors, and with KLF4 in differentiating, but not proliferating, cells to promote expression of specialized keratins required for normal tissue structure and integrity. Our data identify WNT10A as a critical ligand controlling adult epithelial proliferation and region-specific differentiation, and suggest downstream beta-catenin pathway activation as a potential approach to ameliorate regenerative defects in WNT10A patients.
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