Figure 1. Proposed roles for RhoGTPases in Schwann cell myelination.

a) Rac1 and Cdc42 may be required during Schwann cell migration on axons. A negative cross-talk between Merlin/Schwannomin/Nf2 and Rac1 is probably involved in maintaining Rac1-GTP levels low and Nf2 active during early development, to allow for directional migration and elongation of Schwann cells on axons. b) Matching of Schwann cell and axon numbers, together with recognition/segregation of large axons destined for myelination by Schwann cell processes are required for radial sorting of axons and defasciculation. At this stage, merlin/Schwannomin/Nf2 become inactive and Rac1 gets activated at the leading edge of Schwann cell process, to allow extension of radial lamellipodia that ensheath and myelinate axons. Concomitantly, Schwann cell proliferation is ensured by activation of Cdc42 and inactivation of merlin/Schwannomin/Nf2. While full Rac1 activation requires a β1-containing integrin, Cdc42 activation appear to be downstream of the neuregulin/ErbB system. c) Frabin, mutated in Charcot-Marie-Tooth 4H, is a Cdc42 GEF that may be involved in myelin membrane homeostasis through interaction with phosphoinositides (PI). Rho(s) and ROCK may be involved in the regulation of internodes.