Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline

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 robe alone, suggesting that in the absence of robe, comm is no longer required. Comm is expressed on midline cells; Robe is expressed in a dynamic fashion on growth cones and appears to function as an axon guidance receptor. robe function is dosage-sensitive. Overexpression of comm is also dosage-sensitive and leads to a phenotype identical to robe loss-of-function. Comm controls Robe expression; increasing Comm leads to a reduction of Robe protein. The levels of Comm and Robe 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.