PUBLICATION
A G protein-coupled receptor is essential for Schwann cells to initiate myelination
- Authors
- Monk, K.R., Naylor, S.G., Glenn, T.D., Mercurio, S., Perlin, J.R., Dominguez, C., Moens, C.B., and Talbot, W.S.
- ID
- ZDB-PUB-090914-48
- Date
- 2009
- Source
- Science (New York, N.Y.) 325(5946): 1402-1405 (Journal)
- Registered Authors
- Dominguez, Claudia, Mercurio, Sara, Moens, Cecilia, Monk, Kelly, Naylor, Stephen, Perlin, Julie, Talbot, William S.
- Keywords
- none
- MeSH Terms
-
- Cyclic AMP-Dependent Protein Kinases/metabolism
- Signal Transduction
- Early Growth Response Protein 2/genetics
- Early Growth Response Protein 2/metabolism
- Cyclic AMP/metabolism
- Octamer Transcription Factor-6/genetics
- Octamer Transcription Factor-6/metabolism
- Cell Differentiation
- Schwann Cells/cytology
- Schwann Cells/metabolism*
- Myelin Basic Protein/metabolism
- Mutation
- Receptor, ErbB-3/genetics
- Receptor, ErbB-3/metabolism
- Molecular Sequence Data
- Myelin Sheath/physiology*
- Animals
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Axons/physiology
- Axons/ultrastructure
- Lateral Line System/innervation
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism*
- Neuregulin-1/metabolism
- PubMed
- 19745155 Full text @ Science
Citation
Monk, K.R., Naylor, S.G., Glenn, T.D., Mercurio, S., Perlin, J.R., Dominguez, C., Moens, C.B., and Talbot, W.S. (2009) A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science (New York, N.Y.). 325(5946):1402-1405.
Abstract
The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous system. Axonal signals activate expression of specific transcription factors, including Oct6 and Krox20, that initiate myelination in Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are unknown. Using mutational analysis in zebrafish, we found that the G protein-coupled receptor Gpr126 is required autonomously in Schwann cells for myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20 and were arrested at the promyelinating stage. Elevation of cAMP in gpr126 mutants, but not krox20 mutants, could restore myelination. We propose that Gpr126 drives the differentiation of promyelinating Schwann cells by elevating cAMP levels, thereby triggering Oct6 expression and myelination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping