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NIH Research Festival

September 13 – 15, 2017

The novel basic-Helix-Loop-Helix transcription factor AmeloD regulates tooth morphogenesis

Wednesday, September 13, 2017 – Poster Session I
12:00 – 1:30 p.m.

FAES Terrace

NIDCR

DEVBIO-9

Authors

  • Y Chiba
  • B He
  • K Yoshizaki
  • S Fukumoto
  • Y Yamada

Abstract

Tooth development is regulated through the interactions between the dental epithelium and mesenchyme. We identified the novel basic-Helix-Loop-Helix transcriptional factor AmeloD from a tooth germ cDNA library. AmeloD was expressed in inner dental epithelium (IDE) and pre-ameloblasts that actively proliferate and migrate to form enamel. We created AmeloD knockout (KO) mice to analyze the in vivo function of AmeloD. Six-week-old AmeloD KO mice developed enamel hypoplasia, smaller tooth crowns and roots of molars than wild-type (WT) mice. In post-natal day 1 WT incisors, the IDE cells did not express E-cadherin, a negative regulator of cell division and migration. However, in the AmeloD KO teeth, IDE cells expressed E-cadherin, suggesting that cell migration and division were inhibited, resulting in enamel hypoplasia and smaller tooth sizes. For mechanistic analysis in vitro, we used the mouse dental epithelial cell line, CLDE cells. Overexpression of AmeloD suppressed endogenous E-cadherin expression in CLDE cells and promoted cell migration activity. For further analysis of the relationship between migratory property of the dental epithelial cells and tooth morphogenesis, we used Epiprofin KO mice. In Epfn KO mice, dental epithelial cells randomly invade the mesenchymal region, resulting in multiple tooth formation. We found that these invasive dental epithelial cells did not express E-cadherin, but expressed AmeloD. By analyzing tooth phenotypes, we found that Epfn;AmeloD double KO teeth were drastically smaller than Epfn KO teeth via inhibition of cell invasion. Thus, AmeloD acts as a suppressor of E-cadherin to promote IDE cell migration for tooth growth.

Scientific Focus Area: Developmental Biology

This page was last updated on Friday, March 26, 2021

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