Project 1A: Molecular Determinants of Amelogenesis (Papagerakis, Simmer, Franceschi)
Overview: Enamel formation occurs mainly during two well defined stages of development (secretory and maturation stage) that can be followed by investigating the synchronized and stage-specific expression of enamel-specific gene products. The regulation and control of enamel formation (amelogenesis) is complex and current approaches have done little to increase our understanding of it. Our aim is to identify key stage-specific regulatory switches and molecular pathways critical for amelogenesis. Studying how co-expression of these genes is controlled at each specific stage of development will allow us not only to enhance our knowledge of the transcriptional regulation of each of these genes but most importantly to acquire a global understanding of enamel development and its molecular control. This project will enhance our understanding of enamel formation. It might also give new insights on the cross-talks between key molecular pathways that control organogenesis. Ameloblast-specific transcriptional regulators may also be discovered for the first time.
Project 1B: Dental Epithelial Stem Cells and Enamel Regeneration (Papagerakis, Ma)
Overview: Mesenchymal stem cells, which give rise to dentin, bone and cementum, have been isolated and are being studied extensively in the context of tissue regeneration. However, no studies exist on the regenerative potential of epithelial stem cells that could lead to enamel reconstruction. This missing gap is critical because dental enamel, in contrast to bone and dentin, cannot regenerate. Furthermore, without cells that can give rise to ameloblasts, complete biological restoration of human dental crown can not be achieved. Our aim is to identify and characterize dental epithelial stem cells and investigate ways of programming them to become ameloblast-like and able to produce enamel matrix. These studies will lay the foundation for innovative dental regenerative treatments and ultimately will help people with defective or missing enamel.
Project 2A: Developmental Dynamics of Enamel Formation (Papagerakis, Fisher, Simmer)
Overview: Enamel formation is subjected to rhythmical molecular signals that occur on short (24 hour) periods and give rise to cross-striations, or lines perpendicular to each prism. Another more marked disturbance, occurs over longer periods (once every 6-10 days depending upon the individual), and induces the formation of striae of Retzius (SR), which are long-period growth markers. Little is known about the mechanisms regulating enamel formation, but careful analysis of short- and long-period growth lines should permit quantification of the critical parameters that determine crown shape during development. Our aim is (1) to measure growth lines in the crowns of human bicuspids and determine the biological parameters that determine dental crown shape; and (2) to develop mathematically-based 2D and 3D computer models that will simulate the growth of human dental enamel. This information will fill critical gaps in our knowledge of enamel development, improve understanding pathological enamel formation and may also provide a mathematical foundation for dental tissue engineering.
Project 2B: The Circadian Clock of Ameloblasts (Papagerakis, Schnell, Hoogerwerf)
Overview: It has been long suggested that ameloblast gene expression and enamel formation are under circadian control. However, no direct evidence for a “dental” circadian clock exists. It is unknown which of the ameloblast-expressed genes are under circadian control. The expression of clock genes has never been investigated in tooth. The aim of this project is to characterize clock gene expression and role during ameloblast differentiation and enamel formation by using a combination of biological and mathematical approaches. This innovative multidisciplinary approach will allow us to understand how the circadian clock determines gene expression and cell differentiation in the ameloblasts resulting in perfectly regulated enamel formation.
Individuals with background and interest in developmental biology and/or computer modeling that may be interested in participating in any aspect of our projects are welcome to contact us.