Abstract
The migration of Schwann cells is critical for development of peripheral nervous system and is essential for regeneration and remyelination after nerve injury. Although several factors have been identified to regulate Schwann cell migration, intrinsic migratory properties of Schwann cells remain elusive. In this study, based on time-lapse imaging of single isolated Schwann cells, we examined the intrinsic migratory properties of Schwann cells and the molecular cytoskeletal machinery of soma translocation during migration. We found that cultured Schwann cells displayed three motile phenotypes, which could transform into each other spontaneously during their migration. Local disruption of F-actin polymerization at leading front by a Cytochalasin D or Latrunculin A gradient induced collapse of leading front, and then inhibited soma translocation. Moreover, in migrating Schwann cells, myosin II activity displayed a polarized distribution, with the leading process exhibiting higher expression than the soma and trailing process. Decreasing this front-to-rear difference of myosin II activity by frontal application of a ML-7 or BDM (myosin II inhibitors) gradient induced the collapse of leading front and reversed soma translocation, whereas, increasing this front-to-rear difference of myosin II activity by rear application of a ML-7 or BDM gradient or frontal application of a Caly (myosin II activator) gradient accelerated soma translocation. Taken together, these results suggest that during migration, Schwann cells display malleable motile phenotypes and the extension of leading front dependent on F-actin polymerization pulls soma forward translocation mediated by myosin II activity.
Highlights
Myelinating glial cells provide an insulating sheath around axons which is required for the rapid propagation of action potentials and the normal function of nervous systems [1,2]
We used local perfusion of pharmacological agents to single-isolated migrating Schwann cells to examine the roles of cytoskeletal components during Schwann cell migration
We found that during migration, Schwann cell displayed malleable motile phenotypes and extension of leading front dependent on F-actin polymerization pulled soma forward translocation mediated by myosin II activity
Summary
Myelinating glial cells provide an insulating sheath around axons which is required for the rapid propagation of action potentials and the normal function of nervous systems [1,2]. Schwann cells are the major myelinating glial populations in peripheral nervous system. The formation of peripheral myelin by Schwann cells can be divided into three major stages: proliferative, premyelinating and myelinating stages. The proliferative stage is characterized by proliferation and migration of premyelinating Schwann cells [3,4,5,6]. Schwann cells arise from trunk neural crest cells, proliferate, and migrate into peripheral nerve. Schwann cells associate with a single axon, ensheath individual axon and eventually form the myelin sheath [6,7]. Schwann cell migration is critical for development of peripheral nervous system
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