New insights into signaling during myelination in zebrafish

Myelin is a vertebrate adaptation that allows for the rapid propagation of action potentials along axons. Specialized glial cells-oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS)-form myelin by repeatedly wrapping axon segments. Debilitating diseases result from the disruption of myelin, including multiple sclerosis and Charcot-Marie-Tooth peripheral neuropathies. The process of myelination involves extensive communication between glial cells and the associated neurons. The past few years have seen important progress in understanding the molecular basis of the signals that coordinate the development of these fascinating cells. This review highlights recent advances in myelination deriving from studies in the zebrafish model system, with a primary focus on the PNS. While Neuregulin1-ErbB signaling has long been known to play important roles in peripheral myelin development, work in zebrafish has elucidated its roles in Schwann cell migration and radial sorting of axons in vivo. Forward genetic screens in zebrafish have also uncovered new genes required for development of myelinated axons, including gpr126, which encodes a G-protein coupled receptor required for Schwann cells to progress beyond the promyelinating stage. In addition, work in zebrafish uncovered new roles for Schwann cells themselves, including in regulating the boundary between the PNS and CNS and positioning a nerve after its initial outgrowth.