short stop (shot)is required for sensory and motor axons to reach their targets in theDrosophilaembryo. Growth cones inshotmutants initiate at the normal times, and they appear normal with respect to overall morphology and their abilities to orient and fasciculate. However, sensory axons are unable to extend beyond a short distance from the cell body, and motor axons are unable to reach target muscles. Theshotgene encodes novel actin binding proteins that are related to plakins and dystrophin and expressed in axons during development. The longer isoforms identified are predicted to contain an N-terminal actin binding domain, a long central triple helical coiled-coil domain, and a C-terminal domain that contains two EF-hand Ca2+binding motifs and a short stretch of homology to the growth arrest-specific 2 protein. Other isoforms lack all or part of the actin binding domains or are truncated and contain a different C-terminal domain. Only the isoforms containing full-length actin binding domains are detectably expressed in the nervous system.shotis allelic tokakapo, a gene that may function in integrin-mediated adhesion in the wing and embryo. We propose that Shot's interactions with the actin cytoskeleton allow sensory and motor axons to extend.