In the developing tooth, epithelial-mesenchymal interactions initiate signals responsible for the expression of a hierarchical genetic program leading to morphogenesis, cell determination and the expression of gene products associated with control of biomineralization. Understanding the molecular nature of these reciprocal-, instructive-interactions between odontogenic epithelia and mesenchyme which control morphogenesis and terminal phenotype differentiation requires an enhanced molecular analysis of gene expression. Detailed molecular studies of gene expression during mammalian odontogenesis have been hampered by: 1) the absence of isolated cell model systems; 2) a lack of knowledge defining the odontogenic gene repertoire, and 3) ignorance for the temporal- and spatial-restricted pattern of gene expression. Advances to our knowledge now permit the formulation of an experimental strategy designed to analyze mechanisms for oral epithelia determination to the ameloblast phenotype as measured by amelogenin expression. Recent advances in cell and molecular biology now permit enhanced capacity to derive isolated odontogenic cell lineages for analysis of regulated amelogenin transcription, to identify DNAase hypersensitivity sites suggestive of putative regulatory protein-DNA interactions, to derive DNA sequence information for amelogenin and to compare such data to known transcription regulatory motifs and to identify molecular clones for AMEL-specific transcription factors. We will identify the minimal control element regulating amelogenin expression employing progressive deletions of putative regulatory elements by determining their effect on transcription using isolated odontogenic epithelia in transient expression assays. Finally, the DNA binding proteins will be isolated and characterized in order to identify corresponding cDNA clones. These studies will facilitate an understanding of epithelial-mesenchymal instructive signals required for de novo amelogenin expression in a tissue- , temporal- and spatial-restricted fashion during mouse odontogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006988-09
Application #
3220502
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1985-04-01
Project End
1996-09-14
Budget Start
1993-09-15
Budget End
1994-09-14
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Other Domestic Higher Education
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Mounir, Maha M F; Matar, Moustafa A; Lei, Yaping et al. (2016) Recombinant Amelogenin Protein Induces Apical Closure and Pulp Regeneration in Open-apex, Nonvital Permanent Canine Teeth. J Endod 42:402-12
Geng, Shuhui; White, Shane N; Paine, Michael L et al. (2015) Protein Interaction between Ameloblastin and Proteasome Subunit ? Type 3 Can Facilitate Redistribution of Ameloblastin Domains within Forming Enamel. J Biol Chem 290:20661-73
Chavez, Miquella G; Yu, Wenli; Biehs, Brian et al. (2013) Characterization of dental epithelial stem cells from the mouse incisor with two-dimensional and three-dimensional platforms. Tissue Eng Part C Methods 19:15-24
Moshaverinia, Alireza; Ansari, Sahar; Chen, Chider et al. (2013) Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering. Biomaterials 34:6572-9
Lacruz, Rodrigo S; Hacia, Joseph G; Bromage, Timothy G et al. (2012) The circadian clock modulates enamel development. J Biol Rhythms 27:237-45
Lacruz, Rodrigo S; Nakayama, Yohei; Holcroft, James et al. (2012) Targeted overexpression of amelotin disrupts the microstructure of dental enamel. PLoS One 7:e35200
Lacruz, Rodrigo S; Smith, Charles E; Bringas Jr, Pablo et al. (2012) Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling. J Cell Physiol 227:2264-75
Riksen, Elisabeth Aurstad; Kalvik, Anne; Brookes, Steven et al. (2011) Fluoride reduces the expression of enamel proteins and cytokines in an ameloblast-derived cell line. Arch Oral Biol 56:324-30
Snead, Malcolm L; Zhu, Dan-Hong; Lei, Yaping et al. (2011) A simplified genetic design for mammalian enamel. Biomaterials 32:3151-7
Wen, Xin; Cawthorn, William P; MacDougald, Ormond A et al. (2011) The influence of Leucine-rich amelogenin peptide on MSC fate by inducing Wnt10b expression. Biomaterials 32:6478-86

Showing the most recent 10 out of 73 publications