**4. m6A in Axonal and Synaptic Development**

Acute knockdown of *Mettl3* led to remarkable decreases of newborn neurons upon the differentiation of aNSCs, which displayed an immature morphology, with a reduced number of intersections and decreased total dendritic length [12]. In addition, *Mettl3* knockdown also inhibited the morphological development of cultured hippocampal neurons [12]. Fto was enriched in the dendrites and synapses of neurons and can be locally translated into axons [35]. Treatment with a Fto activity inhibitor promoted m6A signals but inhibited axon elongation by regulating the axonal translation of Gap-43 [36]. In addition, transcripts for Roundabout (Robo) family member Robo3.1, an axon guidance receptor, were m6A-modified, and m6A reader Ythdf1 regulated axon guidance via the promotion of the translation of Robo3.1 [37]. Beyond affecting axon growth, m6A also regulates axon regeneration. Peripheral nerve injury induces a dynamic m6A landscape and enhances the expression of mRNAs modified by m6A, including Sox11, Atf3, and Gadd45a [20]. *Mettl14* ablation in mature neurons promoted the translation in the adult dorsal root ganglion (DRG) and reduced the length of the longest neuronal process [20]. Similar effects were also observed in adult DRGs of *Ythdf1*-KO mice.

In addition, m6A modification that was identified in the synaptic transcriptome and in transcripts with m6A peaks in the stop codon but not in the start codon are associated with neurological dysfunction, including intellectual disability, microcephaly, and seizures [38]. m6A level was negatively correlated with transcript abundance in synaptosomal RNAs, suggesting the local degradation of m6A mRNA [38]. Interestingly, m6A peaks in the stop codon did not show a strong effect on the synaptic location of transcripts [38]. Furthermore, in contrast to hypomethylated transcripts, hypermethylated transcripts were highly related to synaptic development and neurological disorders, including intellectual disability, autism, and schizophrenia. [38].
