Macrophage stimulating protein is a target-derived neurotrophic factor for developing sensory and sympathetic neurons

Macrophage stimulating protein (MSP) is a pleiotropic growth factor that signals via the Ron receptor tyrosine kinase. We report that Ron mRNA is expressed by NGF-dependent sensory and sympathetic neurons and that these neurons survive and grow with MSP at different stages of development. Whereas NGF-dependent sensory neurons become increasingly responsive to MSP with age, sympathetic neurons exhibit an early response to MSP that is lost by birth. MSP mRNA expression increases with age in sensory neuron targets and decreases in sympathetic targets. After the phase of naturally occurring neuronal death, significant numbers of NGF-dependent sensory neurons, but not sensory neurons, dependent on other neurotrophins, are lost in mice lacking a functional Ron receptor. These results show that MSP is a target-derived neurotrophic factor for subsets of sensory and sympathetic neurons at different times during their development.