Fig. 1.

Expression of mDISC1 in C. elegans motor neurons causes axon guidance defects. (A–D) Confocal images of the commissural axons from DD and VD motor neurons at L4. In wild-type animals (A and B), all of the commissures reach the dorsal nerve cord. In mDISC1 transgenic animals (C and D), the commissures exhibit guidance defects (arrowheads). Boxed areas in A and C are magnified in B and D, respectively. (Scale bars: A and C, 20 μm; B and D, 10 μm.) (E) The adult mDISC1 animals have an average of 40% axon guidance defect. The L1 transgenic animals exhibit similar percentage of defects, indicating that the phenotype is caused by a defect in the guidance of developing axons rather than to abnormal regrowth from degenerated axons. (F) The axon guidance defects caused by expressing mDISC1 are suppressed by RNAi knockdown of C. elegans homologs of known mammalian DISC1-interacting molecules (n = 25–60). col-86, negative control gene. (G) Incubation of the mDISC1 animals with a PDE4-specific inhibitor, rolipram, suppresses the guidance defects (n = 60). Bars represent the SE. *P < 0.05, **P < 0.001 (Student's t test). In all pictures, anterior is to the left and dorsal is up.