Table 1.
Roles of m6A methylation in the developing CNS
| Roles of m6A methylation in developing CNS | ||||||
|---|---|---|---|---|---|---|
| Lineage development | m6A methyltransferase component involved | Type | m6A-methylated target mRNAs | Mouse models | Neural development function affected | Refs. |
| Cortical neurogenesis | Mettl14 | Writer | Neuronal differentiation-related transcription factors (Pax6, Sox1, Sox2, Emx2, Neurog2, and Neurogenin 2), and proneural genes (Neurod1/2) | Nestin-cre;Mettl14f/f |
1. Temporal specification and cell-cycle progression of NPCs 2. Transcriptional regulation in NSCs 3. Cell-cycle progression of cortical neural progenitors |
[12] |
| Histone acetyltransferase (CBP/p300) | Nestin-cre;Mettl14f/f | 1. Self-renewal of NSCs | [19] | |||
| Ythdf2 | Reader |
Positive regulation of cell differentiation and GTPase activity Negative regulation of JAK-STAT cascade genes (Flrt2/3, Ptprd, and Lrrtm1/4) |
Ythdf2 cKO | 1. Clearance of negative regulators of neurogenesis | [18] | |
| Neural differentiation | Fmrp | Reader | Nuclear retention of m6A-tagged Fmrp target mRNAs | Fmrp KO | 1. Promotion of mRNA nuclear export during neural differentiation | [74] |
| Oligodendrocyte development and myelination | Mettl14 | Writer | Oligodendrocyte lineage genes (Ptprz1, Gsn, and Map2) |
Olig2-cre;Mettl14f/f and CNP-Cre;Mettl14f/f |
1. Differentiation and myelination of OPCs | [57] |
| Prrc2a | Reader | Oligodendroglial transcriptional factor (Olig2) | Nestin-Cre;Prrc2af/f |
1. Proliferation and differentiation of OPCs 2. Stabilization of Olig2 mRNA for oligodendrocyte maturation |
[56] | |
| Cerebellar development | Alkbh5 | Eraser |
Loss of methylated RNAs has been linked to altered cell division (Cenpe), cell cycle (Cdca2), and cell projection organization (Erbb4) genes Hypermethylated RNAs are related to metabolic processes (Ccr5), ion transport (Camk2g), and and axon guidance (Rora) |
Alkbh5 KO |
1. Proliferation and differentiation in the cerebellum 2. Disrupted RNA metabolism of a subset of cell fate determination genes 3. Defected cerebellar development under hypobaric hypoxia |
[60] |
| Neurogenesis in the brain | Fto | Eraser | Loss of Fto led to altered expression of several brain-related neurotrophic factors | Fto KO |
1. Decreased brain size and body weight 2. Reduced pool of NSCs in the SGZ region 3. Reduced proliferation and neuronal differentiation in NSCs 4. Impairment of learning and memory |
[52] |
| Hippocampal neurogenesis | Ythdf1 | Reader | Synaptic plasticity transcripts (Gria1, Grin1, and Camk2a) | Ythdf1 KO |
1. Learning and memory 2. Basal transmission and long-term potentiation at synapses in the hippocampus |
[61] |
| Axon guidance | Ythdf1 | Reader | Axon guidance receptor Robo3.1 | Ythdf1 KO | 1. Axon guidance in spinal commissural axons | [75] |
| Axon regeneration | Ythdf1 | Reader | Axon regeneration-related genes (Tet3 and Gadd45a) | Ythdf1 KO |
1. Axon regeneration in the peripheral nervous system 2. Translation of injury-induced protein 3. Axon regeneration in adult mouse dorsal root ganglions |
[11] |