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学科主题: 口腔医学
题名:
An Nfic-hedgehog signaling cascade regulates tooth root development
作者: Liu, Yang1,2; Feng, Jifan1; Li, Jingyuan1,3; Zhao, Hu1; Ho, Thach-Vu1; Chai, Yang1
关键词: Shh ; Nfic ; Proliferation ; Root development ; Mouse
刊名: DEVELOPMENT
发表日期: 2015-10-01
DOI: 10.1242/dev.127068
卷: 142, 期:19, 页:3374-3382
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Developmental Biology
研究领域[WOS]: Developmental Biology
关键词[WOS]: NUCLEAR FACTOR-I ; CRANIAL NEURAL CREST ; SONIC HEDGEHOG ; BINDING PROTEIN ; STEM-CELLS ; SHH ; TRANSCRIPTION ; ODONTOBLASTS ; MORPHOGENESIS ; GROWTH
英文摘要:

Coordination between the Hertwig′s epithelial root sheath (HERS) and apical papilla (AP) is crucial for proper tooth root development. The hedgehog (Hh) signaling pathway and Nfic are both involved in tooth root development; however, their relationship has yet to be elucidated. Here, we establish a timecourse of mouse molar root development by histological staining of sections, and we demonstrate that Hh signaling is active before and during root development in the AP and HERS using Gli1 reporter mice. The proper pattern of Hh signaling activity in the AP is crucial for the proliferation of dental mesenchymal cells, because either inhibition with Hh inhibitors or constitutive activation of Hh signaling activity in transgenic mice leads to decreased proliferation in the AP and shorter roots. Moreover, Hh activity is elevated in Nfic(-/-) mice, a root defect model, whereas RNA sequencing and in situ hybridization show that the Hh attenuator Hhip is downregulated. ChIP and RNAscope analyses suggest that Nfic binds to the promoter region of Hhip. Treatment of Nfic(-/-) mice with Hh inhibitor partially restores cell proliferation, AP growth and root development. Taken together, our results demonstrate that an Nfic-Hhip-Hh signaling pathway is crucial for apical papilla growth and proper root formation. This discovery provides insight into the molecular mechanisms regulating tooth root development.

语种: 英语
所属项目编号: R01 DE022503 ; R37 DE012711 ; U01 DE024421
项目资助者: National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIH)
WOS记录号: WOS:000365025500012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66434
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, Ostrow 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.Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy & Tooth Regenerat, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Beijing 100050, Peoples R China

Recommended Citation:
Liu, Yang,Feng, Jifan,Li, Jingyuan,et al. An Nfic-hedgehog signaling cascade regulates tooth root development[J]. DEVELOPMENT,2015,142(19):3374-3382.
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