Nfic gene disruption inhibits differentiation of Odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice

Background: Nuclear factor I genes play an important role in the development of the brain, lung, and roots of teeth. We had reported that Nfic-deficient mice form normal crowns, but abnormal roots of molar teeth. However, the mechanism by which the disruption of Nfic gene causes abnormal root formation remains unknown. Methods: To understand this mechanism, the root formation in Nfic-deficient mice was examined and compared to that of wild-type mice by morphological, immunohistochemical, and in situ hybridization analyses. Results: Nfic-deficient mice formed normal Hertwig's epithelial root sheath (HERS) but severely disrupted odontoblast differentiation, leading to the formation of aberrant odontoblasts in the early stage of root formation. They became dissociated and polygonal in shape, lost their orientation and polarity, and did not express dentin sialophosphoprotein. The abnormal roots contained trapped aberrant odontoblasts, thereby resembling osteodentin in overall morphology. No osteoclasts were associated with abnormal roots. Further, the abnormal roots exhibited a decreased number of cementoblasts and cementum formation on the root surface. Conclusions: The loss of Nfic did not interfere with the formation of HERS, but it caused disrupted odontoblast differentiation, which resulted in the formation of short and abnormal roots, and decreased cementum. This finding suggests that root dentin is required for normal cementum formation. Therefore, Nfic may be a key regulator of root odontoblast differentiation and root formation.