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 <i>Dnm2</i> in Schwann cells (SCs) and in oligodendrocytes of mice. <i>Dnm2</i> deletion in developing SCs resulted in severely impaired axonal sorting and myelination onset. Induced <i>Dnm2</i> 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 <i>Dnm2</i> 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 <i>Dnm2</i> deletion in oligodendrocytes.