정한성 (연세대학교 치과대학)

한빛사논문

조회139

연세대학교 치과대학

Exp. Mol. Med., Jul 01 2024, | https://doi.org/10.1038/s12276-024-01264-5 MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis

Dong-Joon Lee^1,2,3,9, Pyunggang Kim^4,9, Hyun-Yi Kim^1,5, Jinah Park⁴, Seung-Jun Lee¹, Haein An⁴, Jin Sun Heo⁴, Min-Jung Lee¹, Hayato Ohshima⁶, Seiya Mizuno⁷, Satoru Takahashi⁷, Han-Sung Jung¹ and Seong-Jin Kim^4,8

¹Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea.

²Department of Oral Histology, Dankook University College of Dentistry, Cheonan 31116, Korea.

³Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea.

⁴GILO Institute, GILO Foundation, Seoul 06668, Korea.

⁵NGeneS Inc., Ansan-si, Gyeonggi-do 15495, Korea.

⁶Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.

⁷Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

⁸Medpacto Inc., Seoul 06668, Korea.

⁹These authors contributed equally: Dong-Joon Lee, Pyunggang Kim.

Corresponding authors

Correspondence to Han-Sung Jung or Seong-Jin Kim.

Abstract

The asymmetric division of stem cells permits the maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows inspection of the role of the stem cell niche to provide specific insights into essential developmental phases. Microtubule-associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with low hardness, as the size of the apical bud was decreased and preameloblasts were shifted to the apical side, resulting in amelogenesis imperfecta. In addition, Mast4 KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis was accelerated with Wnt signal downregulation. Distal-Less Homeobox 3 (DLX3), a critical factor in tooth amelogenesis, is considered to be responsible for the development of amelogenesis imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization site (NLS) that promotes the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role for MAST4 as a critical regulator of the entire amelogenesis process through its control of Wnt signaling and DLX3 transcriptional activity.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-02)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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