Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth

Olfm1, a secreted highly conserved glycoprotein, is detected in peripheral and central nervous tissues and participates in neural progenitor maintenance, cell death in brain, and optic nerve arborization. In this study we identified Olfm1 as a molecule promoting axon growth through interaction with Nogo A receptor (NgR1) complex. Olfm1 is co-expressed with NgR1 in dorsal root ganglia (DRG) and retinal ganglion cells in embryonic and postnatal mice. Olfm1 specifically binds to NgR1 as judged by alkaline phosphatase assay and co-immunoprecipitation. The addition of Olfm1 inhibited the growth cone collapse of DRG neurons induced by myelin-associated inhibitors, indicating that Olfm1 attenuates the NgR1 receptor functions. Olfm1 caused the inhibition of NgR1 signaling by interfering with interaction between NgR1 and its co-receptors, p75NTR or LINGO-1. In zebrafish, inhibition of optic nerve extension by olfm1 morpholino oligonucleotides was partially rescued by dominant negative ngr1 or lingo-1. These data introduce Olfm1 as a novel NgR1 ligand that may modulate the functions of the NgR1 complex in axonal growth.