Lack of mRNA Methylation in Schwann Cells Results in Demyelination and Regenerative Failure
Sari, M. C.; Johnson, A.; Yu, A. T.; Mi, R.; Chen, W.; Hu, X.; Harris, T. G.; Tuffaha, S.; Swarup, V.; Kawaguchi, R.; Ming, G.-L.; Hoke, A.
Show abstract
Schwann cells are essential for peripheral nerve myelination and regeneration. N6-methyladenosine (m6A) RNA methylation, regulated by methyltransferase-like 14 (Mettl14), is a critical post-transcriptional modification, but its role in Schwann cell biology remains unclear. Using a conditional knockout (cKO) mouse model, we investigated the impact of Mettl14-mediated m6A methylation on Schwann cells. Mice born with Schwann cell-specific genetic deletion of Mettl14 developed normally but starting in young adulthood exhibited progressive motor deficits, severe demyelination, and axonal degeneration, confirmed by behavioral assessments and histological analyses. Mettl14-deficient Schwann cells displayed impaired proliferation and mitochondrial dysfunction in vitro. Following sciatic nerve injury, Mettl14 cKO mice showed defective macrophage recruitment, slowed axonal degeneration, and impaired regeneration. These findings suggest that Mettl14-mediated m6A methylation is critical for Schwann cell maintenance but not development. Given that Mettl14 cKO mice developed a demyelinating polyneuropathy, it is possible that manipulation of m6A methylation in Schwann cells is a promising therapeutic strategy targeting peripheral nerve repair and myelination.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Deciphering the molecular landscape of human peripheral nerves: implications for diabetic peripheral neuropathy 96%
- The D84G mutation in STIM1 causes nuclear envelope dysfunction and myopathy in mice 94%
- Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration 93%
Similar papers in this journal
- Ketolysis is Required for the Proper Development and Function of the Somatosensory Nervous System. 95%
- PTEN knockout using retrogradely transported AAVs restores locomotor abilities in both acute and chronic spinal cord injury. 95%
- Sex-dependent effects of peptidylarginine deiminases on neutrophil function and long-term outcomes after spinal cord injury 93%
Similar papers in this journal
- The human ApoE4 variant reduces functional recovery and neuronal sprouting after incomplete spinal cord injury in male mice 94%
- TPPB modulates PKC activity to attenuate neuroinflammation and ameliorate experimental multiple sclerosis 93%
- Retracing Schwann cell developmental transitions in embryonic dissociated DRG/Schwann cell cocultures in mice 92%
Similar papers in this journal
- A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair 96%
- Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun 95%
- Muscle-resident mesenchymal progenitors sense and repair peripheral nerve injury via the GDNF-BDNF axis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.