The tooth root is critical for the function of our dentition because it anchors the tooth to the maxilla or mandible. In addition, the root helps transmit and balance occlusal forces through periodontal ligaments to the jaw bones and serves as a passageway for the neurovascular bundle that supplies blood flow, nutrition, and sensation to our teeth. Importantly, tooth root defects resulting from developmental malformations, pathological conditions and dental treatments are common and significantly compromise quality of life. However, currently we have limited information on the molecular and cellular regulatory mechanisms of crown-to-root transition and tooth root development. Significantly, we have recently identified epithelial and mesenchymal stem cells that are crucial for root development. BMP-mediated SHH signaling provides a niche for Sox2+ epithelial stem cells in molar root development. Moreover, our preliminary study indicated that BMP-mediated HH and FGF signaling in the epithelium may control the crown-to-root transition. We have identified Gli1+ cells as the dental mesenchymal stem cells responsible for controlling root development. In parallel, our preliminary results demonstrate that an epigenetic regulator Ezh2 modulates the transcriptional activity of key genes in the WNT and FGF pathways that are involved in regulating epithelial-mesenchymal interactions to control root formation. We have designed studies to test the hypothesis that BMP-mediated SHH, WNT and FGF signaling control the fate of epithelial and mesenchymal stem cells during root development. This signaling network and Ezh2 exert their functional specificity by regulating specific transcription factors and epithelial-mesenchymal interactions to control root patterning and development.
Our Specific Aims are: (1) to examine how epithelial SHH and FGF, acting downstream of BMP signaling, control the fate of dental epithelial stem cells during root development; (2) to investigate the functional significance of WNT and FGF signaling in regulating specific transcription factors and the fate of CNC-derived MSCs during root development. We will elucidate the molecular mechanism(s) by which signals from the dental mesenchyme control root furcation and development; and (3) to investigate how Ezh2 controls the fate of CNC-derived MSCs during root development. We will investigate the Ezh2-mediated molecular signaling mechanism in regulating tissue-tissue interactions to control root patterning and development.
The tooth root is critical for the function of our dentition because it anchors the tooth to the maxilla or mandible. However, currently we have limited information on the molecular and cellular regulatory mechanisms of crown- to-root transition and tooth root development. We have designed studies to test the hypothesis that BMP- mediated SHH, WNT and FGF signaling and the epigenetic modulator Ezh2 control the fate of epithelial and mesenchymal stem cells during root development.
|Zhao, Hu; Feng, Jifan; Seidel, Kerstin et al. (2018) Secretion of Shh by a Neurovascular Bundle Niche Supports Mesenchymal Stem Cell Homeostasis in the Adult Mouse Incisor. Cell Stem Cell 23:147|
|Li, Jingyuan; Parada, Carolina; Chai, Yang (2017) Cellular and molecular mechanisms of tooth root development. Development 144:374-384|
|Feng, Jifan; Jing, Junjun; Li, Jingyuan et al. (2017) BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice. Development 144:2560-2569|
|Park, Shery; Zhao, Hu; Urata, Mark et al. (2016) Sutures Possess Strong Regenerative Capacity for Calvarial Bone Injury. Stem Cells Dev 25:1801-1807|
|Feng, Jifan; Jing, Junjun; Sanchez-Lara, Pedro A et al. (2016) Generation and characterization of tamoxifen-inducible Pax9-CreER knock-in mice using CrispR/Cas9. Genesis 54:490-6|
|Liu, Yang; Feng, Jifan; Li, Jingyuan et al. (2015) An Nfic-hedgehog signaling cascade regulates tooth root development. Development 142:3374-82|
|Zhao, Hu; Feng, Jifan; Ho, Thach-Vu et al. (2015) The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol 17:386-96|
|Li, Jingyuan; Feng, Jifan; Liu, Yang et al. (2015) BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth. Dev Cell 33:125-35|
|Zhao, H; Chai, Y (2015) Stem Cells in Teeth and Craniofacial Bones. J Dent Res 94:1495-501|
|Zhao, Hu; Feng, Jifan; Seidel, Kerstin et al. (2014) Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor. Cell Stem Cell 14:160-73|
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