An <i>Nfic-</i>hedgehog signaling cascade regulates tooth root development

Liu, Yang; Feng, Jifan; Li, Jingyuan; Zhao, Hu; Ho, Thach-Vu; Chai, Yang

doi:10.1242/dev.127068

Cited by 70 publications

(100 citation statements)

References 53 publications

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“…On the other hand, inhibition of the Shh pathway before molar root initiation, via treatment with Hh inhibitor, also leads to decreased mesenchymal cell proliferation around the HERS and reduced root length . Taken together, these data suggest a dose-dependent role for Shh signaling activity in the regulation of molar root development Liu et al, 2015). As mentioned above, Nfic interacts with Tgfβ signaling during root development, but it is also an important downstream target of Gli1-mediated Hh signaling in the root (Huang et al, 2010).…”

Section: Fgf and Hh Signalingsupporting

confidence: 64%

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Cellular and molecular mechanisms of tooth root development

2017

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The tooth root is an integral, functionally important part of our dentition. The formation of a functional root depends on epithelialmesenchymal interactions and integration of the root with the jaw bone, blood supply and nerve innervations. The root development process therefore offers an attractive model for investigating organogenesis. Understanding how roots develop and how they can be bioengineered is also of great interest in the field of regenerative medicine. Here, we discuss recent advances in understanding the cellular and molecular mechanisms underlying tooth root formation. We review the function of cellular structure and components such as Hertwig's epithelial root sheath, cranial neural crest cells and stem cells residing in developing and adult teeth. We also highlight how complex signaling networks together with multiple transcription factors mediate tissue-tissue interactions that guide root development. Finally, we discuss the possible role of stem cells in establishing the crown-to-root transition, and provide an overview of root malformations and diseases in humans.

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Section: Fgf and Hh Signalingsupporting

confidence: 64%

“…Mutations in DLX3 are also associated with amelogenesis imperfecta hypoplastichypomaturation with taurodontism in humans (Dong et al, 2005). Of note, the ablation of Smad4, Nfic or Wnt10a in mice leads to similar phenotypes Liu et al, 2015;Yang et al, 2015).…”

Section: Root Developmental Defects In Humansmentioning

confidence: 99%

Cellular and molecular mechanisms of tooth root development

2017

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“…Nuclear factor I‐C (NFIC) has long been believed to play an essential role in tooth formation. Disruption of the Nfic gene in mice leads to abnormal tooth roots that are predominantly caused by abnormal odontoblast differentiation and dentin formation during tooth formation (15, 16).…”

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confidence: 99%

Nuclear factor I‐C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling

Zhou

Wang

Qi³

et al. 2017

FASEB j.

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Nuclear factor I-C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasis However, the molecular mechanisms involved have yet to be defined. In the current study, Nfic expression was altered in primary marrow stromal cells and established progenitor lines after adipogenic and osteogenic treatment. Overexpression of Nfic in stromal cells ST2, mesenchymal cells C3H10T1/2, and primary marrow stromal cells inhibited adipogenic differentiation, whereas it promoted osteogenic differentiation. Conversely, silencing of endogenous Nfic in the cell lines enhanced adipogenic differentiation, whereas it blocked osteogenic differentiation. Mechanism investigations revealed that Nfic overexpression promoted nuclear translocation of β-catenin and increased nuclear protein levels of β-catenin and transcription factor 7-like 2 (TCF7L2). Promoter studies and the chromatin immunoprecipitation (ChIP) assay revealed that NFIC directly binds to the promoter of low-density lipoprotein receptor-related protein 5 (Lrp5) and thereafter transactivates the promoter. Finally, inactivation of canonical Wnt signaling in ST2 attenuated the inhibition of adipogenic differentiation and stimulation of osteogenic differentiation by NFIC. Our study suggests that NFIC balances adipogenic and osteogenic differentiation from progenitor cells through controlling canonical Wnt signaling and highlights the potential of NFIC as a target for new therapies to control metabolic disorders like osteoporosis and obesity.-Zhou, J., Wang, S., Qi, Q., Yang, X., Zhu, E., Yuan, H., Li, X., Liu, Y., Li, X., Wang, B. Nuclear factor I-C reciprocally regulates adipocyte and osteoblast differentiation control of canonical Wnt signaling.

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“…BMPs in the dental mesenchyme may participate in the formation of the HERS because BMPs are expressed strongly before root development . NFI‐C has been shown as an important factor for root elongation as Nfic KO mice display no root formation . Here, we observed no difference in the Nfic expression between Bmpr1a cKO and control molars.…”

Section: Discussionmentioning

confidence: 42%

“…I ). The expression levels of Nfic , an important transcription factor that regulates tooth root formation, were also unchanged in the cKO molars. Next, we addressed impacts of the loss of BMP signaling on cell proliferation of odontoblast progenitors.…”

Section: Resultsmentioning

confidence: 96%

BMP‐Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar

et al. 2019

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Dentinogenesis, a formation of dentin by odontoblasts, is an essential process during tooth development. Bone morphogenetic proteins (BMPs) are one of the most crucial growth factors that contribute to dentin formation. However, it is still unclear how BMP signaling pathways regulate postnatal crown and root dentinogenesis. BMPs transduce signals through canonical Smad and non‐Smad signaling pathways including p38 and ERK signaling pathways. To investigate the roles of Smad and non‐Smad signaling pathways in dentinogenesis, we conditionally deleted Bmpr1a, which encodes the type 1A receptor for BMPs, to remove both Smad and non‐Smad pathways in Osterix‐expressing cells. We also expressed a constitutively activated form of Bmpr1a (caBmpr1a) to increase Smad1/5/9 signaling activity without altered non‐Smad activity in odontoblasts. To understand the function of BMP signaling during postnatal dentin formation, Cre activity was induced at the day of birth. Our results showed that loss of BmpR1A in odontoblasts resulted in impaired dentin formation and short molar roots at postnatal day 21. Bmpr1a cKO mice displayed a reduction of dentin matrix production compared to controls associated with increased cell proliferation and reduced Osx and Dspp expression. In contrast, caBmpr1a mutant mice that show increased Smad1/5/9 signaling activity resulted in no overt tooth phenotype. To further dissect the functions of each signaling activity, we generated Bmpr1a cKO mice also expressing caBmpr1a to restore only Smad1/5/9 signaling activity. Restoring Smad activity in the compound mutant mice rescued impaired crown dentin formation in the Bmpr1a cKO mice; however, impaired root dentin formation and short roots were not changed. These results suggest that BMP‐Smad signaling in odontoblasts is responsible for crown dentin formation, while non‐Smad signaling may play a major role in root dentin formation and elongation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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An Nfic-hedgehog signaling cascade regulates tooth root development

Cited by 70 publications

References 53 publications

Cellular and molecular mechanisms of tooth root development

Cellular and molecular mechanisms of tooth root development

Nuclear factor I‐C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling

BMP‐Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar

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