Phosphorylated ERM proteins (red) localize to Schwann cell tips.

In vertebrates, axons are covered with an insulating myelin sheath, punctuated by gaps called nodes of Ranvier where voltage-gated sodium channels cluster. The nodes are essential for propagating action potentials along the axon, but little is known about how they develop. Gatto et al. (page 489) imaged live cell cultures to watch Schwann cells myelinate explanted dorsal root ganglia and discovered a novel growth cone–like structure on the Schwann cells that appears to mediate node formation.

Previous studies have produced a controversy, since the development of nodes seems to require direct contact between Schwann cells and axons in some in vitro systems, but not in others. The authors used a new approach to transfect cultured Schwann cells with fluorescently labeled proteins and watch myelination using time-lapse videography. The Schwann cells initially migrate along axons and resemble aggressively motile fibroblasts, but as the culture matures they assume the bipolar shape characteristic of myelinating cells. Induction of myelination causes the Schwann cell microvillar components to reorganize into structures called caps at the cells' tips.

Schwann cell caps are highly dynamic, and their protein composition and behavior are reminiscent of axonal growth cones. Cap formation requires activation of the Rho pathway, and uncoupling cap formation from myelination interferes with node formation. Efficient node development appears to require a direct interaction between the Schwann cell caps and axons. This coordination may ensure that axons are not completely myelinated.

The results bolster the idea that cell–cell contact is necessary for node formation, and the new methods provide an excellent approximation of in vivo myelination. Nonetheless, Gatto et al. concede that the issue will not be settled until node formation is characterized more fully. The authors are now transfecting cultured Schwann cells with dominant–negative forms of proteins found in the cap to see which components are required for node development. ▪