Abstract

Tooth development is a highly reguated process orchestrated by a number of genes that encode growth factors, transcription factors and extracellular matrix proteins. Molecular mechanisms underlying the noral and abnormal tooth development is not well characterized. We have initiated studies that focus on the candidate genes for the common tooth disorders such as dentinogenesis imperfecta (DGI), dentin dysplasia and osteognensis imperfcta as well as growth factor genes involved in tooth mineralization.Dentin sialophosphoprotein (DSPP) gene is a prime candidate for DGI-II. It encodes a non-collagenous protein that is specifically expressed in odontoblasts and ameloblasts during tooth development. We have clonedand characterized the murine DSPP homolog and targeted its locus mouse embryonic stem cells in order to generate a gene knockout model for DGI-II. Secondly, using the DSPP promoter we targeted expression of candidate genes in developing tooth to delineate their specific roles in tooth development. Studies are underway to characterize the - Dentinogenesis, molecular genetics, gene knockout, growth factors, extracellular matrix, mineralization

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000698-01
Application #
6227919
Study Section
Special Emphasis Panel (FGU)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Bian, Y; Hall, B; Sun, Z-J et al. (2012) Loss of TGF-? signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. Oncogene 31:3322-32
Suzuki, Shigeki; Haruyama, Naoto; Nishimura, Fusanori et al. (2012) Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues. Arch Oral Biol 57:1165-75
Bian, Yansong; Terse, Anita; Du, Juan et al. (2009) Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3K/Akt pathway. Cancer Res 69:5918-26
Gibson, Carolyn W; Li, Yong; Daly, Bill et al. (2009) The leucine-rich amelogenin peptide alters the amelogenin null enamel phenotype. Cells Tissues Organs 189:169-74
Li, Yong; Suggs, Cynthia; Wright, J Timothy et al. (2008) Partial rescue of the amelogenin null dental enamel phenotype. J Biol Chem 283:15056-62
Nandula, Seshagiri R; Amarnath, Shoba; Molinolo, Alfredo et al. (2007) Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. Arthritis Rheum 56:1798-805
Espirito Santo, Alexandre R; Bartlett, John D; Gibson, Carolyn W et al. (2007) Amelogenin- and enamelysin (Mmp-20)-deficient mice display altered birefringence in the secretory-stage enamel organic extracellular matrix. Connect Tissue Res 48:39-45
Honjo, Yasuyuki; Bian, Yansong; Kawakami, Koji et al. (2007) TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma. Cell Cycle 6:1360-6
Heare, T; Alp, N J; Priestman, D A et al. (2007) Severe endothelial dysfunction in the aorta of a mouse model of Fabry disease;partial prevention by N-butyldeoxynojirimycin treatment. J Inherit Metab Dis 30:79-87
Gibson, C W; Yuan, Z A; Li, Y et al. (2007) Transgenic mice that express normal and mutated amelogenins. J Dent Res 86:331-5

Showing the most recent 10 out of 35 publications