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Table 1 Roles of m6A methylation in the developing CNS

From: The m6A epitranscriptome on neural development and degeneration

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
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
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
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
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
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
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