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

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Macrophage stimulating protein (MSP) is a pleiotropic growth factor.
• MSP exerts its function through the Ron receptor tyrosine kinase.
• NGF-dependent sensory and sympathetic neurons are key cell types in the nervous system.

Purpose of the Study:

• To investigate the role of Macrophage stimulating protein (MSP) in the development and survival of NGF-dependent sensory and sympathetic neurons.
• To determine the expression patterns of Ron mRNA and MSP during neuronal development.
• To elucidate the function of the MSP-Ron signaling pathway in neuronal survival, particularly in the context of neuronal death.

Main Methods:

• Analysis of Ron mRNA expression in NGF-dependent sensory and sympathetic neurons.
• Assessment of neuronal survival and growth in response to MSP during different developmental stages.
• Quantification of MSP mRNA expression in neuronal targets.
• Investigation of neuronal survival in mice lacking a functional Ron receptor after the period of naturally occurring neuronal death.

Main Results:

• Ron mRNA is expressed in NGF-dependent sensory and sympathetic neurons.
• MSP promotes the survival and growth of these neurons during specific developmental periods.
• Sensory neurons show increasing responsiveness to MSP with age, while sympathetic neurons lose responsiveness by birth.
• MSP mRNA expression in targets correlates inversely with neuronal responsiveness.
• Loss of functional Ron receptor leads to significant death of NGF-dependent sensory neurons, but not other neurotrophin-dependent sensory neurons.

Conclusions:

• Macrophage stimulating protein (MSP) acts as a target-derived neurotrophic factor for specific subsets of sensory and sympathetic neurons.
• The role of MSP and its responsiveness varies across different neuronal populations and developmental time points.
• The MSP-Ron signaling pathway is critical for the survival of NGF-dependent sensory neurons during postnatal development.