Developing axons find their targets through direct contact with cues i
n the extracellular environment and in response to gradients of diffus
ible factors. The floor plate, a neuroepithelial structure, guides dev
eloping commissural axons in the spinal cord by release of chemoattrac
tants. Floor plate cells express neurokinin-1 receptors, and a transie
ntly appearing subpopulation of commissural axons contains substance P
, the neuropeptide ligand for this receptor, Substance P increases the
amount of axon outgrowth from dorsal horn explants cocultured with fl
oor plate explants. Results of experiments with embryonic rats suggest
that substance P released from pioneering neuronal pathways may regul
ate the release of chemoattractants from floor plate cells.