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学科主题: 口腔医学
题名:
Alk5-Mediated Transforming Growth Factor beta Signaling Acts Upstream of Fibroblast Growth Factor 10 To Regulate the Proliferation and Maintenance of Dental Epithelial Stem Cells
作者: Zhao, Hu1; Li, Sha1; Han, Dong1,2; Kaartinen, Vesa3; Chai, Yang1
刊名: MOLECULAR AND CELLULAR BIOLOGY
发表日期: 2011-05-01
DOI: 10.1128/MCB.01439-10
卷: 31, 期:10, 页:2079-2089
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: LABEL-RETAINING CELLS ; MOUSE INCISORS ; RECEPTOR ALK5 ; I RECEPTOR ; DIFFERENTIATION ; SKIN ; MORPHOGENESIS ; GENERATION ; TEETH
英文摘要:

Mouse incisors grow continuously throughout life. This growth is supported by the division of dental epithelial stem cells that reside in the cervical loop region. Little is known about the maintenance and regulatory mechanisms of dental epithelial stem cells. In the present study, we investigated how transforming growth factor beta (TGF-beta) signaling-mediated mesenchymal-epithelial cell interactions control dental epithelial stem cells. We designed two approaches using incisor organ culture and bromodeoxyuridine (BrdU) pulse-chase experiments to identify and evaluate stem cell functions. We show that the loss of the TGF-beta type I receptor (Alk5) in the cranial neural crest-derived dental mesenchyme severely affects the proliferation of TA (transit-amplifying) cells and the maintenance of dental epithelial stem cells. Incisors of Wnt1-Cre; Alk5(fl/fl) mice lost their ability to continue to grow in vitro. The number of BrdU label-retaining cells (LRCs) was dramatically reduced in Alk5 mutant mice. Fgf10, Fgf3, and Fgf9 signals in the dental mesenchyme were downregulated in Wnt1-Cre; Alk5(fl/fl) incisors. Strikingly, the addition of exogenous fibroblast growth factor 10 (FGF10) into cultured incisors rescued dental epithelial stem cells in Wnt1-Cre; Alk5(fl/fl) mice. Therefore, we propose that Alk5 functions upstream of Fgf10 to regulate TA cell proliferation and stem cell maintenance and that this signaling mechanism is crucial for stem cell-mediated tooth regeneration.

语种: 英语
所属项目编号: R37 DE012711 ; R01 DE014078 ; R01 DE017007
项目资助者: National Institute of Dental and Craniofacial Research, NIH
WOS记录号: WOS:000289936600013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59414
Appears in Collections:北京大学口腔医学院_口腔修复科_期刊论文

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作者单位: 1.Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA
2.Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, Beijing 100081, Peoples R China
3.Univ Michigan, Sch Dent, Ann Arbor, MI 48103 USA

Recommended Citation:
Zhao, Hu,Li, Sha,Han, Dong,et al. Alk5-Mediated Transforming Growth Factor beta Signaling Acts Upstream of Fibroblast Growth Factor 10 To Regulate the Proliferation and Maintenance of Dental Epithelial Stem Cells[J]. MOLECULAR AND CELLULAR BIOLOGY,2011,31(10):2079-2089.
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