title: erbb3 and erbb2 are essential for schwann cell migration and myelination in zebrafish.
abstract: BACKGROUND
  Myelin is critical for efficient axonal conduction in the vertebrate nervous system. Neuregulin (Nrg) ligands and their ErbB receptors are required for the development of Schwann cells, the glial cells that form myelin in the peripheral nervous system. Previous studies have not determined whether Nrg-ErbB signaling is essential in vivo for Schwann cell fate specification, proliferation, survival, migration, or the onset of myelination.
  
  
  RESULTS
  In genetic screens for mutants with disruptions in myelinated nerves, we identified mutations in erbb3 and erbb2, which together encode a heteromeric tyrosine kinase receptor for Neuregulin ligands. Phenotypic analysis shows that both genes are essential for development of Schwann cells. BrdU-incorporation studies and time-lapse analysis reveal that Schwann cell proliferation and migration, but not survival, are disrupted in erbb3 mutants. We show that Schwann cells can migrate in the absence of DNA replication. This uncoupling of proliferation and migration indicates that erbb gene function is required independently for these two processes. Pharmacological inhibition of ErbB signaling at different stages reveals a continuing requirement for ErbB function during migration and also provides evidence that ErbB signaling is required after migration for proliferation and the terminal differentiation of myelinating Schwann cells.
  
  
  CONCLUSIONS
  These results provide in vivo evidence that Neuregulin-ErbB signaling is essential for directed Schwann cell migration and demonstrate that this pathway is also required for the onset of myelination in postmigratory Schwann cells.
authors.affiliation: Department of Developmental Biology, Stanford University, California 94305, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lyons
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Pogoda
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Voas
authors.forename: Ian G
authors.initials: IG
authors.lastname: Woods
authors.forename: Brianne
authors.initials: B
authors.lastname: Diamond
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nix
authors.forename: Naomi
authors.initials: N
authors.lastname: Arana
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jacobs
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001483:Base Sequence; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology*; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D018815:Genes, erbB / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000502:physiology; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D020890:Neuregulin-1; D016590:Aphidicolin; D001973:Bromodeoxyuridine