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.
Highlights
Motor, sensory, and cognitive functions of the nervous system require rapid and refined impulse propagation
We carried out loss-of-function experiments by breeding mice containing loxP-flanked Dnm2 alleles (Sidiropoulos et al, 2012) with Myelin Protein Zero (Mpz)-Cre mice (Feltri et al, 1999a; Feltri et al, 1999b) in which the Cre recombinase is expressed in the Schwann cells (SCs) lineage (Figure 1—figure supplement 1A)
Since dynamin 2 (DNM2) is involved in the fission of vesicles from the plasma membrane during clathrin-mediated endocytosis (CME), we evaluated the rate of CME with a FACS-based transferrin uptake assay using P1-isolated primary SCs from P0-Dnm2KO and control mice
Summary
Sensory, and cognitive functions of the nervous system require rapid and refined impulse propagation. In jawed vertebrates, this is achieved by covering axons with myelin (Weil et al, 2018). Disturbing myelin can lead to disorders in the PNS and/or CNS, including peripheral neuropathies, multiple sclerosis, and leukodystrophies (Nave and Werner, 2014; Saporta and Shy, 2013). Among the CMTs, a dominant intermediate form (DI-CMTB) is caused by mutations at the dynamin 2 (DNM2) locus (Claeys et al, 2009).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
