Distinct roles of Fto and Mettl3 in controlling development of the cerebral cortex through transcriptional and translational regulations

Abstract Proper development of the mammalian cerebral cortex relies on precise gene expression regulation, which is controlled by genetic, epigenetic, and epitranscriptomic factors. Here we generate RNA demethylase Fto methyltransferase Mettl3 cortical-specific conditional knockout mice, detect severe brain defects caused deletion but not knockout. Transcriptomic profiles using sequencing indicate that causes a more dramatic alteration transcription than . Interestingly, conduct ribosome profiling sequencing, find leads to disruption translational regulation mRNAs results in altered translation crucial genes cortical radial glial cells intermediate progenitors. Moreover, elevated significant number mRNAs, particular major components m 6 A methylation. Our findings distinct functions development, uncover profound role regulating control proper development.