Toll, a muscle cell surface molecule, locally inhibits synaptic initiation of the RP3 motoneuron growth cone in Drosophila.

Toll, a transmembrane molecule with extracellular leucine-rich repeats, is dynamically expressed by the Drosophila embryonic musculature. Growth cones of RP3 and other motoneurons normally grow past Toll-positive muscle cells and innervate more distal muscle cells, which have down-regulated their Toll expression. In this study, we show that reciprocal genetic manipulations of Toll proteins can produce reciprocal RP3 phenotypes. In Toll null mutants, the RP3 growth cone sometimes innervates incorrect muscle cells, including those that are normally Toll-positive. In contrast, heterochronic misexpression of Toll in the musculature leads to the same growth cone reaching its correct target region but delaying synaptic initiation. We propose that Toll acts locally to inhibit synaptogenesis of specific motoneuron growth cones and that both temporal and spatial control of Toll expression is crucial for its role in development.