Growth cones turn up concentration gradients of diffusible peripheral target-derived factors

Severed peripheral nerve axons grow across a gap in their pathway to regenerate into the distal nerve stump. At the turn of the century this observation led to the proposal that concentration gradients of factors released from the cells of the distal nerve segment orient the growth of the regenerating axons. Recently, several central nervous system target-derived factors have been shown to direct process outgrowth via concentration gradients of the factors during development. The demonstration of target-derived tropic influences in the peripheral nervous system has however remained elusive. We have examined whether concentration gradients of diffusible factors released by the cells of a length of peripheral nerve influence the outgrowth of adult sensory neuron growth cones in vitro. We demonstrate that the growth cones turn and grow up the concentration gradients, providing evidence for the presence of diffusible peripheral target-derived neurotropic factors that can act in the peripheral nervous system.