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ID 119197
Title Alternative
Nkx2-3 regulates tooth cusp formation and p21 expression
Author
Han, Xue Kyushu University
Yoshizaki, Keigo Kyushu University
Miyazaki, Kanako Kyushu University
Arai, Chieko Kyushu University
Funada, Keita Kyushu University
Yuta, Tomomi Kyushu University
Tian, Tian Kyushu University
Chiba, Yuta Tohoku University
Saito, Kan Tohoku University
Yamada, Aya Tohoku University
Takahashi, Ichiro Kyushu University
Fukumoto, Satoshi Tohoku University
Content Type
Journal Article
Description
Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest– derived mesenchyme. During tooth development, tooth cusps are regulated by precise control of proliferation of cell clusters, termed enamel knots, that are present among dental epithelial cells. The interaction of ectodysplasin-A (EDA) with its receptor, EDAR, plays a critical role in cusp formation by these enamel knots, and mutations of these genes is a cause of ectodermal dysplasia. It has also been reported that deficiency in Nkx2-3, encoding a member of the NK2 homeobox family of transcription factors, leads to cusp absence in affected teeth. However, the molecular role of NKX2-3 in tooth morphogenesis is not clearly understood. Using gene microarray analysis in mouse embryos, we found that Nkx2-3 is highly expressed during tooth development and increased during the tooth morphogenesis, especially during cusp formation. We also demonstrate that NKX2-3 is a target molecule of EDA and critical for expression of the cell cycle regulator p21 in the enamel knot. Moreover, NKX2-3 activated the bone morphogenetic protein (BMP) signaling pathway by up-regulating expression levels of Bmp2 and Bmpr2 in dental epithelium and decreased the expression of the dental epithelial stem cell marker SRY box 2 (SOX2). Together, our results indicate that EDA/NKX2-3 signaling is essential for enamel knot formation during tooth morphogenesis in mice.
Journal Title
Journal of Biological Chemistry
ISSN
00219258
1083351X
NCID
AA1202441X
Publisher
American Society for Biochemistry and Molecular Biology|Elsevier
Volume
293
Issue
38
Start Page
14572
End Page
14584
Published Date
2018-08-08
Rights
This is an Open Access article under the CC BY license(https://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences