A single growth cone is capable of integrating simultaneously presented and functionally distinct molecular cues during target recognition

A variety of cell recognition pathways affect neuronal target recognition. However, whether such pathways can converge at the level of a single growth cone is not well known. The RP3 motoneuron in Drosophila has previously be en shown to respond to the muscle cell surface molecules TOLL and fasciclin III (FAS3), which are normally encountered during RP3 pathfinding in a seq uential manner. TOLL and FAS3, putative "negative" and "positive" recogniti on molecules, respectively, affect RP3 antagonistically Under normal condit ions, TOLL and FAS3 together improve the accuracy of its target recognition . Here, we show that, when presented with concurrent TOLL and FAS3 expressi on, RP3 responds to both, integrating their effects. This was demonstrated most succinctly by single cell visualization methods. When a balance in rel ative expression levels between the two antagonistic cues is achieved, the RP3 growth cone exhibits a phenotype virtually identical to that seen when neither TOLL nor FAS3 is misexpressed. Thus, growth cones are capable of qu antitatively evaluating distinct recognition cues and integrating them to a ttain a net result, in effect responding to the "balance of power" between positive and negative influences. We suggest that the ability to integrate multiple recognition pathways in real-time is one important way in which an individual growth cone interprets and navigates complex molecular environm ents.