Relatively few studies have implicated NT-3 as a chemoattractant agent for sensory and motor axons. Previously noted chemoattractant action of the embryonic mouse maxillary process on trigeminal ganglion neurons (Lumsden and Davies 1986) is now attributed to NT-3 and brain-derived neurotrophic factor (BDNF) (O'Connor et al. 1999). Recently, Tucker et al. (2001) showed that developing sensory and motor axons in limb slice cultures preferentially grow towards neurotrophin-soaked beads instead of following their normal trajectories. Conversely, beads soaked with neurotrophin function-blocking antibodies led to reduction of sensory and motor axon growth towards the limb. In transgenic mice, which over-express NT-3 under the nestin promoter in the central nervous system, the course of the proprioceptive afferents are altered and directed towards the regions with high levels of ectopic NT-3 expression in the spinal cord (Ringstedt et al. 1997). Ringstedt et al. considered the possibility that NT-3 may play a chemoattractant role during the innervation of ventral horns by proprioceptive afferents. However, earlier findings of normal proprioceptive afferent trajectories in chicken embryos despite injection of function-blocking NT-3 antibody into the spinal cord (Oakley et al. 1995) led them to discount this possibility. In that study, though, assays on the effectiveness of antibody perturbation on NT-3-dependent cell survival showed that effectiveness was significant (approximately 90%) but not complete (Oakley et al. 1995). Ringstedt et al. (1997) argue that while central sensory axons may still navigate properly in the absence of NT-3, ectopic expression of NT-3 disrupts their targeting. Recently, another member of the neurotrophin family, BDNF, has been suggested to act as a chemoattractant for sensory axons innervating ear (Tessarollo et al. 2004). In a gene replacement strategy in which BDNF expression was driven by the NT-3 promoter, vestibular axons rerouted towards ectopic sources of BDNF in the cochlea that normally expressed NT-3 and were not innervated by these axons. Ectopic NT-3 supplied using osmotic pumps and adenovirus-mediated expression induce sensory axon growth during regeneration (Zhang et al. 1998, Bradbury et al. 1999, Oudega et al. 1999, Ramer et al. 2002), and induce axonal plasticity of corticospinal axons in injured adult spinal cord (Zhou et al. 2003), where the sprouting axons from the intact site cross the midline towards the NT-3 source on the lesion side of the spinal cord. Our present results are in agreement with these observations, and provide further evidence that NT-3 acts as a chemoattractant for sensory afferents.