commissureless and roundabout lead to complementary mutant phenotypes in which either too few or too many axons cross the midline. The robo;comm double-mutant phenotype is identical to robo alone, suggesting that in the absence of robo, comm is no longer required. Comm is expressed on midline cells; Robo is expressed in a dynamic fashion on growth cones and appears to function as an axon guidance receptor. robo function is dosage-sensitive. Overexpression of comm is also dosage-sensitive and leads to a phenotype identical to robo loss-of-function. Comm controls Robo expression; increasing Comm leads to a reduction of Robo protein. The levels of Comm and Robo appear to be tightly regulated to assure that only certain growth cones cross the midline and that those growth cones that do cross never do so again.