Supplementary Legends
Supplementary Figure 1 Composition and structure of the node and paranode
regions of WT and KO peripheral nerves at 3 weeks. a, The upper panel shows a
teased quadriceps nerve fibre triple-labelled with antibodies against Caspr (red),
sodium channels (Nav) (green) and both neurofascin-155 and neurofascin–186
(Nfasc) (blue). The lower panel shows a fibre double-labelled for -dystroglycan
(DG) (red) and IV-spectrin (IV-spect) (green). The paranodal (Caspr and
neurofascin-155), nodal (sodium channels, neurofascin–186 and IV-spectrin) and
microvillar (-dystroglycan) markers were localized similarly in WT and KO
Schwann cells. b, Western blot of sciatic nerve extracts (20 g protein) showed that
the amounts of IV-spectrin and neurofascin-186 (NF186) (nodal proteins) and
neurofascin-155 (NF155) and Caspr (glial and axonal paranodal proteins respectively)
were higher in the KO compared to WT consistent with the approximate doubling in
the number of nodes and paranodes per unit length in the KO. c, Electron
micrographs of longitudinal sections of quadriceps nerves confirmed that the
microvilli and paranodal axoglial junctions were intact in the KO; scale bar, 1 m.
The inset also shows intact transverse bands at the axoglial junction in both WT and
KO; scale bar, 0.2 m.
Supplementary Figure 2 Conduction velocities, internodal lengths and Cajal bands
in the CMTX mouse, a late-onset demyelinating mutant. a, Conduction velocities and
b, internodal lengths in quadriceps nerves from 3 week-old CMTX mice were not
reduced compared to WT nerves and c, Cajal bands in CMTX sciatic nerves detected
by immunofluorescence staining for S100 appeared normal.
Supplementary Figure 3 Modelling of the sensitivity of nerve conduction velocity
to changes in internodal length. The model was implemented in NEURON1,2 using 10
successive internodal segments. The geometrical parameters utilised for 3 week-old
mouse quadriceps nerve were: axon diameter, 3.0 m; node diameter, 1.7 m;
paranode diameter, 1.7 m; juxtaparanode diameter, 3.0 m; internode diameter, 3.0
m; juxtaparanode length, 33 m; number of myelin lamellae, 60; internodal length,
125-1750 m. The electrical parameters of the nerve fibre were as originally quoted1.
1.
2.
McIntyre, C. C., Richardson, A. G. & Grill, W. M. Modeling the excitability
of mammalian nerve fibers: influence of afterpotentials on the recovery cycle.
J Neurophysiol 87, 995-1006 (2002).
Hines, M. L. & Carnevale, N. T. The NEURON simulation environment.
Neural Comput 9, 1179-209 (1997).