**5. m6A and Gliogenesis**

Astrocytes and oligodendrocytes are two major macroglia cells in the brain that account for at least 50% of brain cells and are involved in diverse biological processes and brain function. In addition, to induce abnormal neurogenesis, acute knockdown of *Mettl3* induces precocious astrocytes upon the differentiation of NSCs [12]. Constitutive deletion of *Mettl14* can significantly reduce astrogenesis in embryonic mice brains [11]. Furthermore, *Ythdf2*-deficient NSCs only generate neuronal cells but not glial cells upon the differentiation [32]. Genetic ablation of *Ythdf2* also increased the sensitivity of newborn neurons to reactive oxygen species stress [32]. Mechanistically, the expression of some transcripts related to neural development and differentiation, axon guidance, and synapse development (i.e., Nrp2, Nrxn3, Flrt2, Ptprd, Ddr2) was remarkably upregulated in *Ythdf2* deficient NSCs [32]. One identified mechanism is that *Ythdf2* deficiency represses m6Amodified mRNA clearance [32]. These findings indicate that m6A writers and reader(s) are essential for the proper temporal progression of neurogenesis and gliogenesis.

In addition to its important roles in astrocytes, differential m6A peaks were detected in transcripts during the differentiation of oligodendrocyte precursor cells (OPCs) to mature

oligodendrocytes. Specific inactivation of *Mettl14* in oligodendrocytes reduces the number of mature oligodendrocytes and, consequently, leads to hypomyelination [39]. Furthermore, *Mettl14* deficiency inhibits oligodendrocyte differentiation, including morphological development, but does not affect OPCs. One potential mechanism is that the loss of *Mettl14* induces the abnormal splicing of myriad RNA transcripts, including neurofascin 155 [39]. Proline-rich coiled-coil 2A (Prrc2a) is a novel m6A reader and is highly expressed in OPCs. *Prrc2a* deficiency reduces the proliferation of OPCs and decreases the expression of oligodendroglial lineage-related transcripts via the direct modulation of the half-life of Olig2 mRNA [40]. Consequently, *Prrc2a*-deficient mice exhibited hypomyelination and impaired locomotive and cognitive abilities [40].
