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

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Myelination is essential for nerve function and involves dynamic membrane remodeling.
• The large GTPase dynamin 2 (DNM2) regulates membrane dynamics, including fission and trafficking.

Purpose of the Study:

• To investigate the role of dynamin 2 (DNM2) in myelination by Schwann cells and oligodendrocytes.
• To explore the consequences of DNM2 loss on peripheral nerve structure and function.

Main Methods:

• Genetic ablation of the Dnm2 gene in mouse Schwann cells (SCs) and oligodendrocytes.
• Analysis of myelination, axonal sorting, and peripheral nerve pathology.
• Assessment of SC survival and cell division.

Main Results:

• Dnm2 deletion in developing SCs impaired axonal sorting and myelination onset.
• Dnm2 deletion in adult SCs led to rapid demyelination and peripheral neuropathy.
• SC loss was partly due to cytokinesis failure; however, surviving SCs effectively remyelinated damaged nerves.
• Dnm2 deletion in oligodendrocytes did not cause major defects in the central nervous system.

Conclusions:

• Dynamin 2 is critical for SC function and peripheral nerve myelination.
• Peripheral nerves exhibit significant self-healing capacity through remyelination by surviving Schwann cells.
• DNM2's role appears specific to peripheral nervous system myelination, with limited impact in the CNS.