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A G protein-coupled receptor is essential for Schwann cells to initiate myelination.

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.

Pubmed ID: 19745155


  • Monk KR
  • Naylor SG
  • Glenn TD
  • Mercurio S
  • Perlin JR
  • Dominguez C
  • Moens CB
  • Talbot WS


Science (New York, N.Y.)

Publication Data

September 11, 2009

Associated Grants

  • Agency: Telethon, Id: GFP03011
  • Agency: NHGRI NIH HHS, Id: HG002995
  • Agency: NINDS NIH HHS, Id: R01 NS050223
  • Agency: NINDS NIH HHS, Id: R01 NS050223
  • Agency: NINDS NIH HHS, Id: R01 NS050223-04
  • Agency: NINDS NIH HHS, Id: R56 NS050223
  • Agency: NINDS NIH HHS, Id: R56 NS050223-05
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Axons
  • Cell Differentiation
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Early Growth Response Protein 2
  • Embryo, Nonmammalian
  • Lateral Line System
  • Molecular Sequence Data
  • Mutation
  • Myelin Basic Protein
  • Myelin Sheath
  • Neuregulin-1
  • Octamer Transcription Factor-6
  • Receptor, ErbB-3
  • Receptors, G-Protein-Coupled
  • Schwann Cells
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins