The ability of neuronal growth cones to be guided by extracellular cues req
uires intimate communication between signal transduction systems and the dy
namic actin-based cytoskeleton at the leading edge. Profilin, a small, acti
n-binding protein, has been proposed to be a regulator of the cell motility
machinery at leading edge membranes. However, its requirement in the devel
oping nervous system has been unknown. Profilin associates with members of
the Enabled family of proteins, suggesting that Profilin might link Abl fun
ction to the cytoskeleton. Here, genetic analysis in Drosophila is used to
demonstrate that mutations in Profilin (chickadee) and Abl (abl) display an
identical growth cone arrest phenotype for axons of intersegmental nerve b
(ISNb). Moreover, the phenotype of a double mutant suggests that these com
ponents function together to control axonal outgrowth.