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KMID : 1036320130350020073
Maxillofacial Plastic and Reconstructive Surgery
2013 Volume.35 No. 2 p.73 ~ p.81
Smad4 Mediated TGF-¥â/BMP Signaling in Tooth Formation Using Smad4 Conditional Knockout Mouse
Yoon Chi-Young

Baek Jin-A
Cho Eui-Sic
Ko Seung-O
Abstract
Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$ ¼ö½Ä À̹ÌÁö/bone morphogenetic protein ($TGF-{\beta}/BMP$ ¼ö½Ä À̹ÌÁö) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ ¼ö½Ä À̹ÌÁö signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4.

Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$ ¼ö½Ä À̹ÌÁö) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$ ¼ö½Ä À̹ÌÁö).

Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$ ¼ö½Ä À̹ÌÁö, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ ¼ö½Ä À̹ÌÁö mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ ¼ö½Ä À̹ÌÁö mice.

Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.
KEYWORD
TGF-beta/BMP, SMAD4, Odontoblast, Ameloblast, Tooth development
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