OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic development

  • Int J Oral Sci. 2026 Apr 6;18(1):32. doi: 10.1038/s41368-026-00431-w.
Zhongyin Zhang  1  2  3 ,  Zerui Shan  1  2  3 ,  Xinyu Chen  1  2  3 ,  Yu Xia  1  2  3 ,  Li Meng  4 ,  Yuxin Zhang  1  2  3 ,  Caihong Wu  1  2  3 ,  Lichan Yuan  5  6  7 ,  Junqing Ma  8  9  10  11  12
Affiliations
  • 1. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
  • 2. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China.
  • 3. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
  • 4. Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China.
  • 5. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. [email protected].
  • 6. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China. [email protected].
  • 7. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. [email protected].
  • 8. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. [email protected].
  • 9. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China. [email protected].
  • 10. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. [email protected].
  • 11. Savaid Stomatology School, Hangzhou Medical College, Hangzhou, China. [email protected].
  • 12. Hangzhou Stomatological Hospital (Zijingang Campus), Hangzhou, China. [email protected].
PMID: 41936590 DOI: 10.1038/s41368-026-00431-w
Abstract

Post-translational modifications (PTMs) have been gradually elucidated in congenital malformations such as cleft palate. Among them, O-GlcNAcylation as a dynamic PTM of proteins regulates various critical biological processes including transcription, translation, and cell fate determination. In this study, a substantial decline in O-linked β-D-N-acetylglucosamine (O-GlcNAc) levels was detected within the palatine plates of all-trans retinoic acid (atRA)-induced cleft palate mice. The role of O-GlcNAc transferase (OGT), the sole enzyme responsible for catalyzing O-GlcNAcylation, was investigated in the process of palatal development. In a zebrafish model, the loss of O-GlcNAc resulted in an elevated prevalence of cleft palate and compromised palatal bone formation. Mechanistically, O-GlcNAcylation of myeloid ecotropic viral integration site 2 (MEIS2), which is mediated by OGT, was found to maintain osteogenic homeostasis by modulating its protein stability through inhibition of ubiquitination. Notably, the serine 237 residue (Ser237) was identified as a critical site for MEIS2 O-GlcNAcylation. Together, the present study uncovers the important function of MEIS2 O-GlcNAcylation in palatal bone development and establishes a novel theoretical framework for understanding the regulatory network of palatal development. This finding may provide novel avenues for the future diagnosis and prevention of cleft palate.

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