Derailed axons get on track

How do growing axons in the central nervous system navigate through the dense jungle of cells and processes that they encounter on the way to their targets? On page 540 of this issue, Bonkowsky et al. show that the choice of pathways for growth cones (the leading edges of growing axons) in the fruit fly Drosophila melanogaster is regulated by a receptor tyrosine kinase known as Derailed (Drl). These results further indicate that, rather than attracting growth cones to the right pathways, Drl causes them to be repelled from the wrong ones. The array of axons in the embryonic Drosophila central nervous system has a ladder-like structure (Fig. 1). Anterior and posterior commissural tracts cross the midline in each body segment, and two longitudinal tracts extend the length of the embryo. Each of the roughly 300 neurons within a unit of this structure is thought to extend its axon along a genetically determined pathway. Most interneurons (neurons that synapse with other neurons) extend axons across the midline of the central nervous system, and attractive and repulsive factors that regulate this fundamental crossing decision have been identified. But axon guidance at the midline involves more than just the decision whether or not to cross. Each commissure contains many distinct pathways, and the growth cone of a particular neuron always follows the same one. The unique sequence of navigational decisions made by its growth cone determines the complex and invariant shape of each axon in the central nervous system