Tooth enamel consists of tightly packed carbonated hydroxyapatite crystals which are organized into rods (prisms) running obliquely to one another in alternating rows. This extraordinary 3D architecture is established during enamel development as a result of the coordinated activity of cellular processes and organic matrix secretion. The present proposal focuses on the role of the unique C-domain of the major enamel matrix gene product, amelogenin, as it pertains to enamel structural organization. In previous studies, we have documented a significant increase in amelogenin C-domain proline and glutamine tandem repeats and prismatic enamel organization during the amphibian/reptile to mammal transition. In the present application, we are using this evolutionary biology approach to decipher the role of the amelogenin C-domain in the evolution of complex enamel structure. As a first step, we have generated frog amelogenin- overexpressing mouse models featuring grossly altered enamel mineral organization and lack of prism formation. Enamel thickness was further decreased and prisms were lacking when amel-overexpressors were crossed with amel null mice. In order to understand how specific domains of the amelogenin gene might affect alterations in enamel biomineralization during vertebrate evolution, we are now submitting a research plan to determine the effect of amelogenin C-domain evolution as it relates to enamel matrix organization, enamel crystal and prism formation. Our studies are designed to test the hypothesis that complex mammalian enamel architecture is a result of enamel matrix structure sophistication facilitated by amelogenin C-domain evolution.

Public Health Relevance

The purpose of this research project is to identify key factors in tooth enamel formation. Tooth enamel in frog teeth is thin, little organized, and soft, while tooth enamel in mammals'features sophisticated organization and is thicker and harder than frog enamel. Here we are comparing the difference between frog and mouse enamel to identify key differences in enamel formation on a protein level. We are interested in the center portion of the major enamel protein, amelogenin. We believe that this center portion plays an important role in enamel formation and we will use a number of models to find out whether our thinking is accurate. Among those model systems will be experiments in which we will mix this protein with crystal growth solutions and experiments in which we manipulate the major gene in mice. We hope that one day our approach will lead to new ways of repairing human teeth.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MOSS-K (09))
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Wan, Jason
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University of Illinois at Chicago
Schools of Dentistry
United States
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Pandya, Mirali; Rosene, Lauren; Farquharson, Colin et al. (2017) Intravesicular Phosphatase PHOSPHO1 Function in Enamel Mineralization and Prism Formation. Front Physiol 8:805
Pandya, Mirali; Lin, Tiffani; Li, Leo et al. (2017) Posttranslational Amelogenin Processing and Changes in Matrix Assembly during Enamel Development. Front Physiol 8:790
Pandya, Mirali; Liu, Hui; Dangaria, Smit J et al. (2017) Integrative Temporo-Spatial, Mineralogic, Spectroscopic, and Proteomic Analysis of Postnatal Enamel Development in Teeth with Limited Growth. Front Physiol 8:793
Mao, Yelin; Satchell, Paul G; Luan, Xianghong et al. (2016) SM50 repeat-polypeptides self-assemble into discrete matrix subunits and promote appositional calcium carbonate crystal growth during sea urchin tooth biomineralization. Ann Anat 203:38-46
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Wang, Xinping; Xing, Zeli; Zhang, Xichen et al. (2013) Alternative Splicing of the Amelogenin Gene in a Caudate Amphibian, Plethodoncinereus. PLoS One 8:e68965
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Lu, Xuanyu; Ito, Yoshihiro; Kulkarni, Ashok et al. (2011) Ameloblastin-rich enamel matrix favors short and randomly oriented apatite crystals. Eur J Oral Sci 119 Suppl 1:254-60
Zhang, Xu; Diekwisch, Thomas G H; Luan, Xianghong (2011) Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse. Eur J Oral Sci 119 Suppl 1:270-9
Diekwisch, Tom (2011) Evolution and ameloblastin. Eur J Oral Sci 119 Suppl 1:293-7

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