HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR IS AN AXONAL CHEMOATTRACTANT AND A NEUROTROPHIC FACTOR FOR SPINAL MOTOR-NEURONS

In the embryonic nervous system, developing axons can be guided to the ir targets by diffusible factors secreted by their intermediate and fi nal cellular targets. To date only one family of chemoattractants for developing axons has been identified. Grafting and ablation experiment s in fish, amphibians, and birds have suggested that spinal motor axon s are guided to their targets in the limb in part by a succession of c hemoattractants made by the sclerotome and by the limb mesenchyme, two intermediate targets that these axons encounter en route to their tar get muscles. Here we identify the limb mesenchyme-derived chemoattract ant as hepatocyte growth factor/scatter factor (HGF/SF), a diffusible ligand for the c-Met receptor tyrosine kinase, and we also implicate H GF/SF at later stages as a muscle-derived survival factor for motoneur ons. These results indicate that, in addition to functioning as a mito gen, a motogen, and a morphogen in nonneural systems, HGF/SF can funct ion as a guidance and survival factor in the developing nervous system .