Figure 4.

Inhibition of Hmg-CoA reductase phenocopies hmgcs1^vu57. A, The cholesterol biosynthetic pathway. Inhibitors used for this study are shown in red. B–D, Lateral views, with dorsal up, of trunk spinal cords of living 3 dpf larvae. Dorsally migrated OPCs occupy positions close to the DLF (dotted line) of wild-type (B). OPCs migrate past the DLF in vu57 mutant larva (C) and a wild-type larvae treated with Atorvastatin (D). E–J, Images of hindbrains viewed from dorsal with anterior to the left, of larvae processed for in situ RNA hybridization. By contrast to wild-type (E) and similar to a hmgcs1^vu57 mutant larva (F), a wild-type larva treated with Atorvastatin expresses little plp1a RNA (G). Atorvastatin also blocks mbp expression (H–J). K, Graph showing mbp RNA expression levels in 4 dpf larvae measured by quantitative RT-PCR. DMSO-treated control larvae express mbp at slightly lower level than untreated wild-type. Atorvastatin-treated wild-type larvae express mbp at levels similar to hmgcs1^vu57 mutant larvae (n = 4 biological replicates consisting of 10–15 larvae for each measurement; *p = 0.0101, ***p < 0.0005, unpaired two-tailed Student's t test). Error bars represent SEM.