Fig. 8

Chronic dynein inhibition disrupts MBP protein translation in cultured oligodendrocytes and disrupts myelination in zebrafish. (A) A model shows that transport of Mbp mRNA granules by microtubule-based motors precedes local translation and recruitment of ribosomes. (B) Quantification of the percentage of DIV3 oligodendrocytes treated for 21 h with 5 μM ciliobrevin that express MBP protein demonstrate that a lower percentage of ciliobrevin-treated cells (42%) are positive for MBP protein compared with control cells (63%, P < 0.001) and DMSO-treated cells (62%, P < 0.001). Of these MBP-containing cells, only 8.5% of ciliobrevin-treated cells highly expressed MBP protein compared with 29% (P < 0.001) and 27% (P < 0.001) in control and DMSO-treated cells. (C) Cells treated with 5 μM ciliobrevin for 21 h were costained with single-molecule FISH probes against Mbp mRNA and with a monoclonal antibody against MBP protein. MBP protein images (Middle) show examples of high expressers (arrows) in control cells and low expressers (arrowheads) in ciliobrevin-treated cells (n = 2 biological replicates using primary cultures from two different animals, four coverslips, 23–32 fields of view per group).