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Ift88 regulates enamel formation via involving Shh signaling

Research output: Contribution to journalArticlepeer-review

Takehisa Kudo, Maiko Kawasaki, Katsushige Kawasaki, Fumiya Meguro, Jun Nihara, Izumi Honda, Madoka Kitamura, Akira Fujita, Kazuaki Osawa, Kaya Ichikawa, Takahiro Nagai, Yoko Ishida, Paul T. Sharpe, Takeyasu Maeda, Isao Saito, Atsushi Ohazama

Original languageEnglish
JournalOral Diseases
Accepted/In press2022

Bibliographical note

Funding Information: This research was funded by the Japan Society for the Promotion of Science (JSPS; 26293421). We thank Dr. Finsa Tisna Sari for support and assistance. Publisher Copyright: © 2022 Wiley Periodicals LLC.

King's Authors


Objectives: The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear. Materials and Methods: We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88fl/fl;K14Cre). Results: Ift88fl/fl;K14Cre mice showed premature abrasion in molars. A pattern of enamel rods which is determined at secretory stage, was disorganized in Ift88 mutant molars. Many amelogenesis-related molecules expressing at the secretory stage, including amelogenin and ameloblastin, enamelin, showed significant downregulation in Ift88 mutant molar tooth germs. Shh signaling is essential for amelogenesis, which was found to be downregulated in Ift88 mutant molar at the secretory stage. Application of Shh signaling agonist at the secretory stage partially rescued enamel anomalies in Ift88 mutant mice. Conclusion: Findings in the present study indicate that the function of the primary cilia via Ift88 is critical for the secretory stage of amelogenesis through involving Shh signaling.

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