METTL5 regulates cranial suture fusion via Wnt signaling

作     者：Kexin Lei Ruoshi Xu Qian Wang Qiuchan Xiong Xinyi Zhou Qiwen Li Dutmanee Seriwatanachai Shuibin Lin Chenchen Zhou Quan Yuan Kexin Lei;Ruoshi Xu;Qian Wang;Qiuchan Xiong;Xinyi Zhou;Qiwen Li;Dutmanee Seriwatanachai;Shuibin Lin;Chenchen Zhou;Quan Yuan

作者机构：State Key Laboratory of Oral DiseasesNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Department of Oral BiologyFaculty of DentistryMahidol UniversityBangkok 73170Thailand Center for Translational MedicinePrecision Medicine InstituteThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China 

出 版 物：《Fundamental Research》 (自然科学基础研究（英文版）)

年 卷 期：2023年第3卷第3期

页      面：369-376页

核心收录：

学科分类：1003[医学-口腔医学] 10[医学] 

基　　金：supported by grants from the National Natural Science Founda-tion of China(82125006) Sichuan Science&Technology Program(2021YFH0015). 

主　　题：METTL5 N6-methyladenosine Cranial suture Osteogenic differentiation Mesenchymal stem cells 

摘      要：METTL5 is a methyltransferase that mediates eukaryotic 18S ribosomal RNA m^(6)A modification,and its mutations lead to intellectual disability,microcephaly,and facial dysmorphism in patients.However,the role of METTL5 in craniofacial development remains poorly understood.This study demonstrates that Mettl5 knockout mice exhibit poor ossification,widened cranial sutures,and a cleidocranial dysplasia-like phenotype.Deletion of Mettl5 leads to increased proliferation and decreased osteogenic differentiation of suture mesenchymal stem cells.Mechanistically,we find that Wnt signaling is significantly downregulated after Mettl5 knockout.Overall,we reveal an essential role of METTL5 in craniofacial development and osteogenic differentiation of suture mesenchymal stem cells,making METTL5 a potential diagnostic and therapeutic target for craniofacial developmental diseases.