membrane-extending and microvilli-generating capacities of Schwann cells suggest an integral role for cytoskeletal remodeling in Schwann cell maturation. This possibility is supported by the growth cone-like properties displayed by the terminal processes of migrating Schwann cell precursors in vivo

INTRODUCTION Axons ensheathed with myelin propagate action potentials in a saltatory manner resulting in significantly accelerated conduction velocity and reduced energy requirements. In the peripheral nervous system (PNS), myelin is elaborated by Schwann cells. Their precursors emerge from the neural crest early in development and distribute amongst elongating axons, where they proliferate and migrate with advancing axons (Jessen et al., 1994; Wanner et al., 2006). As development proceeds they form discrete Schwann cell families that encircle bundles of axons, where they continue to proliferate as well as extend and retract radially oriented processes between axons, ultimately ensheathing all large caliber axons in a process referred to as radial sorting (Webster et al., 1973; Grove et al., 2007; Woodhoo et al., 2009) (for a review, see Woodhoo and Sommer, 2008). To initiate axon ensheathment, a Schwann cell develops a longitudinal groove that deepens as it extends processes circumferentially to fully enwrap the axon (Webster, 1971; Webster et al., 1973; Webster, 1984). Through mechanisms that remain poorly understood (Bunge et al., 1989), the Schwann cell membrane spirally wraps around the axon, following which, interlamellar Schwann cell cytoplasm is extruded and the apposing membrane layers are stabilized by myelin-associated proteins (Wood et al., 1990). In addition to their seemingly lamellipodialike mesaxons, Schwann cells generate microvilli at the electrophysiologically specialized nodes of Ranvier that are located between successive myelin sheaths (Gatto et al., 2003). The migratory, membrane-extending and microvilli-generating capacities of Schwann cells suggest an integral role for cytoskeletal remodeling in Schwann cell maturation. This possibility is supported by the growth cone-like properties displayed by the terminal processes of migrating Schwann cell precursors in vivo (Wanner et al., 2006) and by both the structure and composition of the mesaxons that are elaborated by myelinating Schwann cells in vitro (Bacon et al., 2007). Also, in Schwann cell-neuron cocultures, myelin formation is attenuated when actin polymerization is disrupted by cytochalasin D (Fernandez-Valle et al., 1997). Similarly, in mice, myelin formation is attenuated when the Cdc42 or Rac1 GTPase cytoskeletal regulators are deleted (Nodari et al., 2007; Benninger et al., 2007). Additionally, Rho GTPase and its kinase, ROCK, have been implicated in Schwann celland/or oligodendrocyte-mediated myelination (Melendez-Vasquez et al., 2004) (for a review, see Feltri et al., 2008). Although a link between cytoskeletal dynamics and myelination is widely appreciated, the specific effectors that modulate cytoskeletal reorganization in developing and myelinating Schwann cells are not well defined. However, one likely effector is the neuronal Wiskott-Aldrich syndrome protein [N-WASp; also known Development 138, 1329-1337 (2011) doi:10.1242/dev.058677 © 2011. Published by The Company of Biologists Ltd