Hertwig's epithelial root sheath (HERS) consists of bilayeredcells derived from the inner and outer dentalepithelia and plays important roles in tooth root formation aswell as in the maintenance and regeneration of periodontaltissues. With regards to the fate of HERS, and although previousreports have suggested that this entails the formationof epithelial rests of Malassez, apoptosis or an epithelialmesenchymaltransformation (EMT), it is unclear whatchanges occur in the epithelial cells in this structure. Thisstudy examined whether HERS cells undergo EMT using akeratin-14 (K14) cre:ROSA 26 transgenic reporter mouse.The K14 transgene is expressed by many epithelial tissues,including the oral epithelium and the enamel organ. Adistinct K14 expression pattern was found in the continuousHERS bi-layer and the epithelial diaphragm were visualizedby detecting the β-galactosidase (lacZ) activity in 1 weekpostnatal mice. The 2 and 4 week old mice showed afragmented HERS with cell aggregation along the rootsurface. However, some of the lacZ-positive dissociated cellsalong the root surface were not positive for pan-cytokeratin.These results suggest that the K14 transgene is a valuablemarker of HERS. In addition, the current data suggest thatsome of the HERS cells may lose their epithelial propertiesafter fragmentation and subsequently undergo EMT.