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Int. J. Oral Sci., Dec 01 2025, 17 (1) | https://doi.org/10.1038/s41368-025-00405-4
Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling
Minjae Kyeong 1 †, Ju-Kyung Jeong 2 †, Dinuka Adasooriya 1, Shiqi Kan 1, Jiwoo Kim 1, Jieun Song 3, Sihyeon Park 3, Suyeon Je 3, Seok Jun Moon 1,4, Young-Bum Park 5, Hyuk Wan Ko 3 *, Eui-Sic Cho 2 * and Sung-Won Cho 1 *
1Department of Oral Biology, BK21 FOUR Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea
2Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Jeonbuk National University School of Dentistry, Jeonju, South Korea
3Department of Biochemistry, Yonsei University College of Life Science and Biotechnology, Seoul, South Korea
4Taste Research Center, Yonsei University College of Dentistry, Seoul, South Korea
5Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, South Korea
†These authors contributed equally
*Corresponding authors: correspondence to Hyuk Wan Ko, Eui-Sic Cho or Sung-Won Cho
Abstract
Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1-/-;PCS1-MRCS1△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
논문정보
- Research article
- 2025년 12월 (BRIC 등록일 2025-12-02)
- 국내 연구진
- 생명과학 > 발생생물학
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