Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs.

The molecular mechanisms controlling the ability of motor axons to recognize their appropriate muscle targets were dissected using Drosophila genetics to add or subtract Netrin A, Netrin B, Semaphorin II, and Fasciclin II alone or in combination. Fas II and Sema II are expressed by all muscles where they promote (Fas II) or inhibit (Sema II) promiscuous synaptogenesis. NetB is expressed by a subset of muscles where it attracts some axons and repels others. However, growth cones in this system apparently do not rely solely on single molecular labels on individual targets. Rather, these growth cones assess the relative balance of attractive and repulsive forces and select their targets based on the combinatorial and simultaneous input of multiple cues.