N6-methyladenosine (m6A) RNA methylation mediated by methyltransferase complex subunit WTAP regulates amelogenesis

N6-methyladenosine (m6A) RNA methylation, one of the most widespread posttranscriptional modifications in eukary-otes, plays crucial roles in various developmental processes. The m6A modification process is catalyzed by a methyl-transferase complex that includes Wilms tumor 1-associated protein (WTAP) as a key component. Whether the develop-ment of dental enamel is regulated by m6A RNA methylation in mammals remains unclear. Here, we reveal that WTAP is widely expressed from the early stage of tooth development. Specific inactivation of Wtap in mouse enamel epithelium by the Cre/loxp system leads to serious developmental defects in amelogenesis. In Wtap conditional KO mice, we determined that the differentiation of enamel epithelial cells into mature ameloblasts at the early stages of enamel development is affected. Mechanistically, loss of Wtap inhibits the expression of Sonic hedgehog (SHH), which plays an important role in the generation of ameloblasts from stem cells. Together, our findings provide new insights into the functional role of WTAP-mediated m6A methylation in amelogenesis in mammals.

Automated summary

This study reveals the functional role of WTAP-mediated m6A RNA methylation in mammalian amelogenesis. The results show that WTAP is widely expressed in the early stages of tooth development, and its loss leads to severe developmental defects in enamel formation. Mechanistically, WTAP loss inhibits the expression of Sonic hedgehog. These findings provide new insights into the importance of m6A methylation in enamel development.