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Axonal neuregulin-1 regulates myelin sheath thickness.

In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve conduction velocity. Neuronal overexpression of Nrg1 induces hypermyelination and demonstrates that Nrg1 type III is the responsible isoform. We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size.

Pubmed ID: 15044753

Authors

  • Michailov GV
  • Sereda MW
  • Brinkmann BG
  • Fischer TM
  • Haug B
  • Birchmeier C
  • Role L
  • Lai C
  • Schwab MH
  • Nave KA

Journal

Science (New York, N.Y.)

Publication Data

April 30, 2004

Associated Grants

None

Mesh Terms

  • Animals
  • Axons
  • Ganglia, Spinal
  • Gene Targeting
  • Genes, erbB
  • Genes, erbB-2
  • Heterozygote
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Neurological
  • Myelin Sheath
  • Neural Conduction
  • Neuregulin-1
  • Protein Isoforms
  • Receptor, Epidermal Growth Factor
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Schwann Cells
  • Sciatic Nerve
  • Signal Transduction