Understanding how instructed determination of phenotypes through reciprocal epithelial-mesenchymal interactions remains a significant problem area in developmental craniofacial biology. An excellent model for examining instructive epithelial-ectomesenchymal interactions is the developing tooth organ. In the developing tooth, ectomesenchymal signals determine epithelium to express de novo amelogenin gene transcript and translation products. We have identified five aims to characterize differential gene expression during instructive or permissive epithelial-mesenchymal interactions: i) determine when and where nascent amelogenin gene transcription and translation products appear during in vivo mouse mandibular first molar development; ii) determine when and where amelogenin gene transcript and translation products appear during the in vitro development of mouse mandibular first molar tooth organs, in the presence and absence of serum; iii) determine when and where amelogenin gene transcript and translation products are expressed during cap stage dental ectomesenchyme-instructed mouse foot pad epithelial differentiation to ameloblasts; iv) in tooth like heterotypic recombinants composed of tooth mesenchyme and foot pad epithelium determine if keratin gene expression is either arrested prior to, or is concurrent with, amelogenin gene expression; and v) to characterize the molecular basis of dental ectomesenchyme-derived signals for the instruction of epithelial differentiation to ameloblasts. The methods for analysis are nucleic acid hybridization to a cDNA probe to the 26 kilodalton amelogenin gene product and immunodetection of amelogenin polypeptides using a rabbit anti-mouse amelogenin antibody. The successful completion of these specific aims will produce significant insight into the mechanisms operant during epithelial-mesenchymal interactions in craniofacial morphogenesis. A more complete understanding of this problem area will enhance the clinical management and perhaps modes of intervention in abnormal craniofacial development.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Schools of Dentistry/Oral Hygn
Los Angeles
United States
Zip Code
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