Figure 4.
4E-BP1-dependent translation downstream of Akt-mTOR signaling promotes myelination. A, Schematic illustrating the mechanism by which 4E-BPs promote translation initiation and the function disruption strategy. B, Representative images of single 5 dpf spinal cord oligodendrocytes expressing controls or 4E-BP1 manipulation with or without simultaneous mTOR pathway manipulations. Scale bar, 10 µm. Quantification of myelin sheath length (C), number (D), or cumulative myelin sheath length (E). Violin plot solid lines indicate median. Dashed lines indicate 25th and 75th percentiles. Overall significance was assessed using the Kruskal–Wallis test: sheath length, p < 1 × 10−12, h = 458.4; sheath number, p = 8.62 × 10−6, h = 33.44; cumulative sheath length, p < 1 × 10−12, h = 86.76. Orange dots represent individual data points. Sample sizes: WT, 19 fish, 19 cells, 190 sheaths; 4EBP1wt, 18 fish, 18 cells, 169 sheaths; 4EBP1T37/46A, 22 fish, 22 cells, 179 sheaths; myrAkt, 16 fish, 16 cells, 155 sheaths; 4EBP1T37/46A + myrAkt, 17 fish, 17 cells, 126 sheaths; mtor−/−, 17 fish, 17 cells, 148 sheaths; 4EBP1T37/46A + mtor−/−, 20 fish, 20 cells, 154 sheaths. p values are pairwise Mann–Whitney tests with Bonferroni–Holm correction for multiple comparisons.