Enamel is the outer covering of teeth and is unique in that it is the hardest tissue in our body and one of the few human tissues that cannot regenerate. This inability for human enamel to regenerate is attributed to the loss of ameloblasts or enamel-forming cells and their precursor cells upon eruption of teeth into the oral cavity. Thus, it would be powerful if we could direct adult stem cells that normally do not produce enamel to differentiate into ameloblasts and unravel the molecular mechanisms involved. Two novel genetically modified mouse lines developed in my laboratory allows us to induce inactivation of the Isl1 gene (which leads to ectopic enamel formation in adult mice) or deletion of cells expressing Isl1 (which allows us to remove putative dental epithelial stem cells for functional analysis). By analyzing context dependent roles of Isl1 during mouse incisor renewal, we will advance our molecular and cellular understanding of stem cell specification, ameloblast differentiation, and enamel mineralization - pre-requisite for future innovations and improvements to current diagnostic, preventive, and therapeutic methods in dentistry.
? PUBLIC HEALTH RELEVANCE Enamel is the outer covering of teeth, the main line of defense against decay, and one of the few human tissues that cannot regenerate therefore, comprehensive understanding of enamel formation is pre-requisite for a potential lifetime of healthy teeth, whether by steering proper formation or applying stem cell-based therapy. Using two novel genetically modified mouse lines developed in my laboratory, we have the unprecedented ability to induce inactivation of the Isl1 gene (which leads to the generation of ectopic enamel in adult mice) or deletion of cells expressing Isl1 (which will allow for functional analysis of putative dental epithelial stem cells). Thus, we will determine the context dependent roles of Isl1 and advance our understanding of the cellular and molecular mechanisms of stem cell specification and enamel formation, information that may be exploited to improve upon diagnostic, preventive, and therapeutic methods in dentistry.