Nr-CAM is a neuronal
cell adhesion molecule (CAM) belonging to the
immunoglobulin superfamily that has been implicated as a
ligand for another CAM,
axonin-1, in guidance of commissural axons across the floor plate in the spinal cord. Nr-CAM also serves as a neuronal receptor for several other cell surface molecules, but its role as a
ligand in neurite outgrowth is poorly understood. We studied this problem using a chimeric Fc-fusion
protein of the extracellular region of Nr-CAM (Nr-Fc) and investigated potential neuronal receptors in the developing peripheral nervous system. A recombinant Nr-CAM-Fc fusion
protein, containing all six Ig domains and the first two
fibronectin type III repeats of the extracellular region of Nr-CAM, retains cellular and molecular binding activities of the native
protein. Injection of Nr-Fc into the central canal of the developing chick spinal cord in ovo resulted in guidance errors for commissural axons in the vicinity of the floor plate. This effect is similar to that resulting from treatment with
antibodies against
axonin-1, confirming that
axonin-1/Nr-CAM interactions are important for guidance of commissural axons through a spatially and temporally restricted Nr-CAM positive domain in the ventral spinal cord. When tested as a substrate, Nr-Fc induced robust neurite outgrowth from dorsal root ganglion and sympathetic ganglion neurons, but it was not effective for tectal and forebrain neurons. The peripheral but not the central neurons expressed high levels of
axonin-1 both in vitro and in vivo. Moreover,
antibodies against
axonin-1 inhibited Nr-Fc-induced neurite outgrowth, indicating that
axonin-1 is a neuronal receptor for Nr-CAM on these peripheral
ganglion neurons. The results demonstrate a role for Nr-CAM as a
ligand in axon growth by a mechanism involving
axonin-1 as a neuronal receptor and suggest that dynamic changes in Nr-CAM expression can modulate axonal growth and guidance during development.