During peripheral nerve development, each segment of a myelinated axon is matched with a single Schwann cell. Tight regulation
of Schwann cell movement, proliferation and differentiation is essential to ensure that these glial cells properly associate
with axons. ErbB receptors are required for Schwann cell migration, but the operative ligand and its mechanism of action have
remained unknown. We demonstrate that zebrafish Neuregulin 1 (Nrg1) type III, which signals through ErbB receptors, controls
Schwann cell migration in addition to its previously known roles in proliferation and myelination. Chimera analyses indicate
that ErbB receptors are required in all migrating Schwann cells, and that Nrg1 type III is required in neurons for migration.
Surprisingly, expression of the ligand in a few axons is sufficient to induce migration along a chimeric nerve constituted
largely of nrg1 type III mutant axons. These studies also reveal a mechanism that allows Schwann cells to fasciculate axons regardless of
nrg1 type III expression. Time-lapse imaging of transgenic embryos demonstrated that misexpression of human NRG1 type III results
in ectopic Schwann cell migration, allowing them to aberrantly enter the central nervous system. These results demonstrate
that Nrg1 type III is an essential signal that controls Schwann cell migration to ensure that these glia are present in the
correct numbers and positions in developing nerves.