Semaphorin III can induce death in sensory neurons

Semaphorin III has been described to function as a guidance molecule direct ing growing axons to their target. However, its effect on the neuron cell b ody has not been characterized. Semaphorin III has a highly dynamic express ion pattern, which generally corroborates a chemorepellent guidance functio n, but also suggests additional functions, different from axon guidance. A number of studies show that some sensory neurons are eliminated, while thei r axons are still pathfinding. In this study we have investigated whether S emaphorin III also influences the survival of sensory neurons. We here pres ent evidence that Semaphorin III can function in vitro as selective death f actor for NGF-dependent sensory neurons. Semaphorin III induces a type of c ell death that is characterized by slow onset, cell body shrinking, nuclear condensation, and TUNEL-positive staining of dying neurons. These are all hallmarks of neuronal apoptosis. We also show evidence that neurons can mod ulate the response to Semaphorin III. The novel function described here may also be relevant in vivo, contributing to active elimination of neurons du ring development or after injury.