Secretion of intrinsic cues controls repulsion of nociceptive neurons

The longstanding question of how the pattern of skin sensory innervation arises led us to investigate the behavior of rat DRG sensory axonal outgrowth. Outgrowing neurites from NGF-stimulated DRGs placed in close vicinity demonstrated repulsive behavior in the form of turning responses. In contrast, NT3-dependent neurites intermingled, as did neurites cultured without collagen embedding. These observations raise the possibility that secretion and not contact repulsion is the dermatome-building mechanism of nociceptive territories. Further experiments with functional antibodies against known secreted guidance molecules had no blocking effect. Our data provide evidence that the segmented pattern of skin nociceptive sensory maps is supported by unknown intrinsic cues released from the sensory axons themselves.