Title: The Role of Islet1 in Amelogenesis During Mouse Incisor Renewal
Clare Lee (Presenter)
Bin Zhang, UCSF
Andrew Jheon, UCSF
Objectives: Islet1 (Isl1) is a transcription factor that functions in the development and maintenance of several organs and tissues. Inactivation of Isl1 during mouse development leads to ectopic lingual incisor enamel and premature labial incisor enamel. The objective of this study was to determine whether we could induce the same phenotype with inactivation of Isl1 in adult mice.
Methods: To characterize the effects of spatial and temporal inactivation of Isl1 in amelogenesis during incisor renewal, we generated Krt14CreER;Isl1fl/fl mice and induced inactivation of epithelial Isl1. Adult Krt14CreER;Isl1fl/fl mice were injected with tamoxifen at day 0 and day 1, and chased for 6 days. We also performed lineage tracing experiments in adult Isl1CreER :RFP (red fluorescent protein) mice to visualize ISL1+ cells. Mice not exposed to tamoxifen served as controls. Control and experimental (i.e., tamoxifen-treated) mice were analyzed for expression of RFP, amelogenin (AMEL), and ameloblastin (AMBN).
Results: When epithelial Isl1 was inactivated in adult mice, we observed ectopic expression of AMEL and AMBN on the lingual side and premature expression on the labial side of the incisor. Expression of RFP indicated progeny of ISL1+ cells, and these cells were largely present in the stratum intermedium cells.
Conclusions: We observed ectopic and premature amelogenesis with Isl1 inactivation in adult Krt14CreER;Isl1fl/fl mice. Thus, we have developed the first mouse line in which ectopic incisor enamel can be induced in adult mice. Furthermore, lineage tracing experiments visualized ISL1+ cells, which includes progeny of ISL1+ cells, another step towards mechanistic understanding of the role of Isl1 in amelogenesis.