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.
Michailov
Galin V
GV
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
Sereda
Michael W
MW
Brinkmann
Bastian G
BG
Fischer
Tobias M
TM
Haug
Bernhard
B
Birchmeier
Carmen
C
Role
Lorna
L
Lai
Cary
C
Schwab
Markus H
MH
Nave
Klaus-Armin
KA
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure*; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology; D005727:Ganglia, Spinal / Q000737:chemistry; D018390:Gene Targeting; D018815:Genes, erbB; D018734:Genes, erbB-2; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008959:Models, Neurological; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure*; D009431:Neural Conduction; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000502:physiology; D012583:Schwann Cells / Q000502:physiology; D012584:Sciatic Nerve / Q000737:chemistry; D015398:Signal Transduction
D066246:ErbB Receptors; D020890:Neuregulin-1; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3