Distribution of neurotrophin receptors in the mouse neuromuscular system.

ABSTRACT

The neurotrophins are a family of secreted proteins with critical roles in regulation of many aspects of neural development, survival and maintenance. Their actions on neural tissue are thought to be mediated by interaction with high affinity (trk family members) or low affinity (p75NTR) cell surface receptors. In general, neurotrophins are considered to be supplied in limiting quantity by cells of a target tissue or synaptic partner. To date, alpha motoneurons have been shown surprisingly indifferent to loss of neurotrophic factors. Direct evidence for supply of a critical motoneuron factor(s) by skeletal muscle and a specific uptake mechanism in vivo remains elusive. We wished to directly establish whether targets in the periphery might be potential sources of neurotrophic support for motoneurons by examining whether neurotrophin receptors are present on motoneuron nerve terminals. We have used immunofluorescence techniques with a panel of antibodies against known neurotrophin receptors (trk A, trk B, trk C, p75NTR) to map the locations of these receptors in the developing neuromuscular system of mice from our neurotrophin-3 (NT-3) knockout colony. To our surprise, we failed to locate immunoreactivity for any of these receptors in association with motor nerve endplates or terminal intramuscular axon branches, although they were found in association with a population of unidentified cells. We believe this result indicates that the neurotrophic relationship between alpha motoneurons and their target cells is not a simple one of neurotrophin supply by skeletal muscle cells and its uptake at the neuromuscular junction.