Integrin receptors for extracellular matrix transmit mechanical and biochemical information through molecular connections to the actin cytoskeleton and to several intracellular signaling pathways. In Caenorhabditis elegans, integrins are essential for embryonic development, muscle cell adhesion and contraction, and migration of nerve cell axons and gonadal distal tip cells. To identify key components involved in distal tip cell migration, we are using an RNA interference (RNAi)-based genetic screen for deformities in gonad morphogenesis. We have found that talin, a cytoskeletal-associated protein and focal adhesion component, is expressed in the distal tip cell and plays a central role in regulating its migration. Reduction of talin expression caused severe defects in gonad formation because of aberrant distal tip cell migration and also disrupted oocyte maturation and gonad sheath cell structure. Contractile muscle cells showed disorganization of the actin cytoskeleton leading to complete paralysis, a phenotype that was also observed with depletion of pat-2 and pat-3 integrins. These in vivo analyses show that talin is required not only for strong adhesion and cytoskeletal organization by contractile cells, but also for dynamic regulation of integrin signals during cell migration. In addition, induction of distal tip cell migration defects by bacterial RNAi in C. elegans provides an effective screen to identify genes involved in integrin signaling and function.