Ift88 regulates enamel formation via involving Shh signaling

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

doi:10.1111/odi.14162

Ift88 regulates enamel formation via involving Shh signaling

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^*

^*Corresponding author for this work

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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, (Ift88^fl^/^fl;K14Cre). Results: Ift88^fl^/^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.

Original language	English
Journal	Oral Diseases
DOIs	https://doi.org/10.1111/odi.14162
Publication status	Accepted/In press - 2022

Keywords

enamel formation
Ift88
primary cilia
Shh signaling

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10.1111/odi.14162

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@article{9f4adb293b334ff4af87e354f01ad968,

title = "Ift88 regulates enamel formation via involving Shh signaling",

abstract = "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.",

keywords = "enamel formation, Ift88, primary cilia, Shh signaling",

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

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: {\textcopyright} 2022 Wiley Periodicals LLC.",

year = "2022",

doi = "10.1111/odi.14162",

language = "English",

journal = "Oral Diseases",

issn = "1354-523X",

publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Ift88 regulates enamel formation via involving Shh signaling

AU - Kudo, Takehisa

AU - Kawasaki, Maiko

AU - Kawasaki, Katsushige

AU - Meguro, Fumiya

AU - Nihara, Jun

AU - Honda, Izumi

AU - Kitamura, Madoka

AU - Fujita, Akira

AU - Osawa, Kazuaki

AU - Ichikawa, Kaya

AU - Nagai, Takahiro

AU - Ishida, Yoko

AU - Sharpe, Paul T.

AU - Maeda, Takeyasu

AU - Saito, Isao

AU - Ohazama, Atsushi

N1 - 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.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - enamel formation

KW - Ift88

KW - primary cilia

KW - Shh signaling

UR - http://www.scopus.com/inward/record.url?scp=85125379074&partnerID=8YFLogxK

U2 - 10.1111/odi.14162

DO - 10.1111/odi.14162

M3 - Article

C2 - 35189017

AN - SCOPUS:85125379074

SN - 1354-523X

JO - Oral Diseases

JF - Oral Diseases

ER -

Ift88 regulates enamel formation via involving Shh signaling

Abstract

Keywords

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