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TISSUE-SPECIFIC STEM CELLS |
aStowers Institute for Medical Research, Kansas City, Missouri, USA;
bLaboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA;
cDepartment of Oral Biology, School of Dentistry, University of Missouri-Kansas City, Kansas City, Missouri, USA;
dDepartment of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kansas, USA
Key Words. Hair follicle • Stem cells • BMP • ß-Catenin • Wnt • PTEN • Akt
Correspondence: Linheng Li, Ph.D., Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, Missouri 64110, USA. Telephone: 816-926-4081 (ext. 4083); Fax: 816-926-2023; e-mail: lil{at}stowers-institute.org
Received November 4, 2005;
accepted for publication August 17, 2006.
First published online in STEM CELLS EXPRESS September 7, 2006.
Epithelial stem cells (EP-SCs) located in the bulge region of a hair follicle (HF) have the potential to give rise to hair follicle stem/progenitor cells that migrate down to regenerate HFs. Bone morphogenetic protein (BMP) signaling has been shown to regulate the HF cycle by inhibiting anagen induction. Here we show that active BMP signaling functions to prevent EP-SC activation and expansion. Dynamic expression of Noggin, a BMP antagonist, releases EP-SCs from BMP-mediated restriction, leading to EP-SC activation and initiation of the anagen phase. Experimentally induced conditional inactivation of the BMP type IA receptor (Bmpr1a) in EP-SCs leads to overproduction of HF stem/progenitor cells and the eventual formation of matricomas. This genetic manipulation of the BMP signaling pathway also reveals unexpected activation of ß-catenin, a major mediator of Wnt signaling. We propose that BMP activity controls the HF cycle by antagonizing Wnt/ß-catenin activity. This is at least partially achieved by BMP-mediated enhancement of transforming growth factor-ß-regulated epithelial cell-specific phosphatase (PTEN) function. Subsequently, PTEN, through phosphatidyl inositol 3-kinase-Akt, inhibits the activity of ß-catenin, the convergence point of the BMP and Wnt signaling pathways.
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