METTL5 regulates cranial suture fusion via Wnt signaling.

METTL5 is a methyltransferase that mediates eukaryotic 18S ribosomal RNA m6A 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.