Figure 2: Role of m⁶A in neural development.

(A) Mettl3 conditional knockout (cKO) mice are characterized by cerebellar hypoplasia resulting from significantly enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer. Upon Mettl3 cKO, key developmental genes, and apoptosis-associated genes, were upregulated as a result of extended mRNA half-lives, whilst aberrant splicing events on synapse-associated genes were also observed. (B) Mettl14 cKO in embryonic mouse brains results in loss of m⁶A and prolonged radial glial cell cycle. Transcription factors are marked with m⁶A, which results in their degradation. This is required to maintain proper cortical neurogenesis. (C) Loss of YTHDF2 in neural stem cells results in reduced proliferation and differentiation. Furthermore, neurons were shown to exhibit less neurite outgrowth and shorter neurites. (D) Prrc2a binds and stabilizes to the CDS of m⁶A-marked oligodendrocyte transcription factor 2 (Olig2) mRNA, a key oligodendroglial lineage-determining transcription factor. Prrc2a cKO resulted in significant hypomyelination.