Neuronal Neuregulin 1 type III directs Schwann cell migration

Perlin, J.R., Lush, M.E., Stephens, W.Z., Piotrowski, T., and Talbot, W.S.
Development (Cambridge, England)   138(21): 4639-4648 (Journal)
Registered Authors
Lush, Mark E., Perlin, Julie, Piotrowski, Tatjana, Talbot, William S.
myelin, neuregulin, schwann cell, zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Biomarkers/metabolism
  • Cell Differentiation/physiology
  • Cell Movement/physiology*
  • Cell Proliferation
  • Humans
  • Molecular Sequence Data
  • Neuregulin-1/genetics
  • Neuregulin-1/metabolism*
  • Neurons/cytology
  • Neurons/metabolism
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism*
  • Receptor, ErbB-2/genetics
  • Receptor, ErbB-2/metabolism
  • Schwann Cells/cytology
  • Schwann Cells/physiology*
  • Sequence Alignment
  • Transplantation Chimera
  • Zebrafish/anatomy & histology*
  • Zebrafish/embryology
21965611 Full text @ Development
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.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes