Schwann cells reposition a peripheral nerve to isolate it from postembryonic remodeling of its targets.

Although much is known about the initial construction of the peripheral nervous system (PNS), less well understood are the processes that maintain the position and connections of nerves during postembryonic growth. Here, we show that the posterior lateral line nerve in zebrafish initially grows in the epidermis and then rapidly transitions across the epidermal basement membrane into the subepidermal space. Our experiments indicate that Schwann cells, which myelinate axons in the PNS, are required to reposition the nerve. In mutants lacking Schwann cells, the nerve is mislocalized and the axons remain in the epidermis. Transplanting wild-type Schwann cells into these mutants rescues the position of the nerve. Analysis of chimeric embryos suggests that the process of nerve relocalization involves two discrete steps - the degradation and recreation of the epidermal basement membrane. Although the outgrowth of axons is normal in mutants lacking Schwann cells, the nerve becomes severely disorganized at later stages. In wild-type embryos, exclusion of the nerve from the epidermis isolates axons from migration of their targets (sensory neuromasts) within the epidermis. Without Schwann cells, axons remain within the epidermis and are dragged along with the migrating neuromasts. Our analysis of the posterior lateral line system defines a new process in which Schwann cells relocate a nerve beneath the epidermal basement membrane to insulate axons from the postembryonic remodeling of their targets.