erbb3 and erbb2 Are Essential for Schwann Cell Migration and Myelination in Zebrafish

Autor: Matthew G. Voas, William S. Talbot, Hans-Martin Pogoda, Jennifer Jacobs, Ian G. Woods, Naomi Arana, Rebecca Nix, Brianne Diamond, David A. Lyons
Rok vydání: 2005
Předmět:
DNA
Complementary
Neuregulin-1
Molecular Sequence Data
Schwann cell
Biology
General Biochemistry
Genetics and Molecular Biology
Schwann cell proliferation
03 medical and health sciences
ErbB Receptors
Myelin
0302 clinical medicine
Aphidicolin
ErbB
Cell Movement
medicine
Animals
ERBB3
In Situ Hybridization
Myelin Sheath
Zebrafish
030304 developmental biology
0303 health sciences
Base Sequence
Agricultural and Biological Sciences(all)
Biochemistry
Genetics and Molecular Biology(all)
Genes
erbB
Schwann cell migration
Chromosome Mapping
Sequence Analysis
DNA
Genes
erbB-2
Immunohistochemistry
medicine.anatomical_structure
nervous system
Bromodeoxyuridine
Mutation
Cancer research
Neuregulin
Schwann Cells
General Agricultural and Biological Sciences
030217 neurology & neurosurgery
Cell Division
Signal Transduction
Zdroj: Current Biology. 15(6):513-524
ISSN: 0960-9822
DOI: 10.1016/j.cub.2005.02.030
Popis: Summary 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.
Databáze: OpenAIRE
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