BMP4 signaling mediates Zeb family in developing mouse tooth.

Tooth morphogenesis is regulated by sequential and reciprocal interaction between oral epithelium and neural-crest-derived ectomesenchyme. The interaction is controlled by various signal molecules such as bone morphogenetic protein (BMP), Hedgehog, fibroblast growth factor (FGF), and Wnt. Zeb family is known as a transcription factor, which is essential for neural development and neural-crest-derived tissues, whereas the role of the Zeb family in tooth development remains unclear. Therefore, this study aimed to investigate the expression profiles of Zeb1 and Zeb2 during craniofacial development focusing on mesenchyme of palate, hair follicle, and tooth germ from E12.5 to E16.5. In addition, we examined the interaction between Zeb family and BMP4 during tooth development. Both Zeb1 and Zeb2 were expressed at mesenchyme of the palate, hair follicle, and tooth germ throughout the stages. In the case of tooth germ at the cap stage, the expression of Zeb1 and Zeb2 was lost in epithelium-separated dental mesenchyme. However, the expression of Zeb1 and Zeb2 in the dental mesenchyme was recovered by Bmp4 signaling via BMP4-soaked bead and tissue recombination. Our results suggest that Zeb1 and Zeb2, which were mediated by BMP4, play an important role in neural-crest-derived craniofacial organ morphogenesis, such as tooth development.