Schwann cells, but not Oligodendrocytes, Depend Strictly on Dynamin 2 Function

Abstract

Myelination requires extensive plasma membrane rearrangements, implying that molecules controlling membrane dynamics play prominent roles. The large GTPase dynamin 2 (DNM2) is a well-known regulator of membrane remodeling, membrane fission, and vesicular trafficking. Here, we genetically ablated Dnm2 in Schwann cells (SCs) and in oligodendrocytes of mice. Dnm2 deletion in developing SCs resulted in severely impaired axonal sorting and myelination onset. Induced Dnm2 deletion in adult SCs caused a rapidly-developing peripheral neuropathy with abundant demyelination. In both experimental settings, mutant SCs underwent prominent cell death, at least partially due to cytokinesis failure. Strikingly, when Dnm2 was deleted in adult SCs, non-recombined SCs still expressing DNM2 were able to remyelinate fast and efficiently, accompanied by neuropathy remission. These findings reveal a remarkable self-healing capability of peripheral nerves that are affected by SC loss. In the central nervous system, however, we found no major defects upon Dnm2 deletion in oligodendrocytes.

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

“…of SCs, the remaining SCs were able to replenish the SC population, highlighting the apparent self-healing capacity of peripheral nerves (Gerber et al, 2019). These studies suggest that stimulating the intrinsic regenerative capacity of SCs is likely the best approach for improving nerve repair.…”

“…The lack of need for a further stem cell population to produce new SCs is further supported by studies that demonstrated that dedifferentiated SCs possess unlimited proliferative capacity (Mathon, Malcolm, Harrisingh, Cheng, & Lloyd, ). Moreover, a recent study reported that following depletion of ~70% of SCs, the remaining SCs were able to replenish the SC population, highlighting the apparent self‐healing capacity of peripheral nerves (Gerber et al, ). These studies suggest that stimulating the intrinsic regenerative capacity of SCs is likely the best approach for improving nerve repair.…”

Dimeric prion protein ligand activates Adgrg6 but does not rescue myelinopathy of PrP-deficient mice

“…Electrophysiological investigations were performed on the sciatic nerve of mice treated with FT2Fc or control treatment. Mice were anesthetized with Ketamine-Xylazine and electrophysiological investigations were performed as previously described (Zielasek et al, 1996;Gerber et al, 2019). The investigators were blinded as to the treatment and strain of the mice during the tests as well as post-hoc analyses.…”

Fibulin 5, a human Wharton's jelly-derived mesenchymal stem cells-secreted paracrine factor, attenuates peripheral nervous system myelination defects through the Integrin-RAC1 signaling axis

“…Of note, the actin dynamics of SCs is essential throughout the processes of myelination. [66][67][68] In the initial stages of the myelination, actin polymerization is necessary for SCs to wrap and elongate the axons. 61,69 Then, SCs express MBP and widely distribute them for myelin sheathing of axons by forcing actin depolymerization.…”