Disruption of the Nfic Gene Causes Aberrant Odontoblast Differentiation and Abnormal Dentin Formation
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The phylogeneticall y conserved nuclear factor 1 (NFI) gene fami ly encodes s ite-specific tra nscription factors essential for the development of a number of organ syst ems. There are four NFI genes in mamma ls (Nfi a , Nfib, Nfi c, and Nfix) and single NFI genes in Drosophila melanogaster, Caenorhabdi t is elegans, Anopheles spP. ‘ and other simpl e animals. It was reported that Nfia-defici ent mice exhi bit agenesis of the corpus call osum and other forebrain defects , wher eas Nfib-defi cient mice possess unique defects in lung ma turation and fo rebrain defect. Recently, it was also found that Nfic-defi cient mice exhibit agenesis of mo l ar서 roots and severe incisor defects. In the present study, we investigat ed the possible role of NFI-C in odon toblast diffe rent ia tion and root dentin formation using the innovative and invalua ble Nfic knockout mice model Nfi c-defi cient mice showed a berrant odontoblast differentiation and consequentl y abnormal dentin formation, while other t issues/organs in the body including ameloblasts of the enamel organ a ppeared to be unaffec ted and normal One of the most st r iking changes observed in these aberrant odontoblasts was t he absence of in tercellular junctions beLween them, r esulting in di ssociation of the cells and loss of th eir cellular polarity a nd organi zation. Surprisingly, these cells became trapped in dentin-like minerali zed t issue and thus their overa ll morphology r esembled osteoblasts and os t eocyt es. There was also an increased apoptotic activity in Nfic-deficient mice. These findings strongly s uggest ed that NFI -C plays a key role in odon tob last differentiation and survival in a cell type-specific manner.