Fig. 4: ADAR1 activity is required to control myelin formation within sciatic nerves at P4.

a Toluidine blue-staining and b, c electron micrographs of transverse sections of sciatic nerves from control and HtPA-Cre; Adar1^fl/fl mutant mice, illustrating the almost total absence of myelin in the mutants compared to controls. In mutants, the axons were surrounded by cytoplasmic extensions of the SCs, but the latter stalled at this promyelinating stage (b and insets shown in c). Note that a minority of mutant SCs myelinate axons properly (see b) along with absence of sign of axonal degeneration or B- or T-cell or macrophage invasion in the mutants compared to controls. Scale bars: 10 µm (a), 2 µm (b), 500 nm (c). d Quantifications performed from TEM pictures to count myelinated axons number per nerve, the SCs number per square millimeter and the distribution of axon diameter in controls (gray) and HtPA-Cre; Adar1^fl/fl mutants (blue). Data of the three graphs represent mean ± SEM of n = 3 mice/group (Statistical differences between the groups were determined using t test (asterisks represent p value: ***p < 0.001, or Kolmogorov–Smirnov test, p values indicated on the graph). e DAPI (blue)/YFP(green), DAPI (blue)/MBP(green) or DAPI (blue)/Activated-Caspase 3 (red) immunostaining performed on sections of sciatic nerves from control and HtPA-Cre; Adar1^fl/fl mutant mice along with the quantification of % of caspase-3-positive cells among YFP-positive cells. Data represent mean ± SEM. Statistical differences between the groups (n = 5 independent sections of four controls and n = 8 independent sections of five mutants) was determined using t test (asterisks represent p value: ***p < 0.001). Scale bar: 50 μm. f Relative expression of various SCs markers in sciatic nerve from control (gray) and HtPA-Cre; Adar1^fl/fl mutant (blue) mice analyzed by RT-qPCR. All data represent mean ± SEM (n = 5 or 6 controls and n = 3 mutants depending on tested genes). Statistical differences between the groups were determined using t test (asterisks represent p value: ***p < 0.001). For (d–f), source data are provided as a Source data file.