ErbB signaling has a role in radial sorting independent of Schwann cell number.

In the peripheral nervous system, Schwann cells make myelin, a specialized sheath that is essential for rapid axonal conduction of action potentials. Immature Schwann cells initially interact with many axons, but, through a process termed radial sorting, eventually interact with one segment of a single axon as promyelinating Schwann cells. Previous studies have identified genes that are required for Schwann cell process extension and proliferation during radial sorting. Previous analyses also show that ErbB signaling is required for Schwann cell proliferation, myelination, radial sorting, and the proper formation of unmyelinated Remak bundles. Because ErbB signaling and Schwann cell proliferation are both required during radial sorting, we sought to determine if the primary function of ErbB signaling in this process is to regulate Schwann cell proliferation or if ErbB signaling also controls other aspects of radial sorting. To address this question, we applied small molecule inhibitors in vivo in zebrafish to independently block ErbB signaling and proliferation. Ultrastructural analysis of treated animals revealed that both ErbB signaling and Schwann cell proliferation are required for radial sorting in vivo. ErbB signaling, however, is required for Schwann cell process extension, while Schwann cell proliferation is not. These results provide in vivo evidence that ErbB signaling plays a direct role in process extension during radial sorting, in addition to its role in regulating Schwann cell proliferation.