The proposed research program seeks to address the biological role of neuroleukin (NLK) in vivo. NLK is expressed st high levels in muscle and maintains the survival of subpopulations of spinal and sensory neurons in short term cultures. The hypothesis of be tested is that NLK is the target-derived growth that maintains the survival in vivo of spinal motor neurons and proprioceptive sensory neurons. Initial studies will seek to define the neurons responsive to NLK in culture by examining the expression of neuron subtype specific enzyme markers. The effect of NLK on motor neuron survival and cholinergic maturation will be assessed in spinal cord cultures. Motor neurons will be identified in culture by retrograde labeling with fluorescent dyes and the effect of NLK on their survival and expression of choline acetyltransferase (CAT) will be examined. Carbonic anhydrase (CAnh) is an enzyme marker for muscle spindle afferents in vivo and will be evaluated as an enzyme marker for NLK sensitive sensory neurons in culture. Autoimmune deprivation by placental transport of maternal antibody to NLK will be used to examine if NLK is required for normal development of the spinal cord and sensory ganglia. Tissue samples from NLK deprived neonatal animals and from chick, mouse, or rat embryos treated with NLK will be analyzed for alterations in the expression of CAT in spinal cord and of CAnh in sensory ganglia. Positive findings will be confirmed by histochemistry, immuno- cytochemistry, or morphometry. The effect of NLK on motor axon ultraterminal sprouting also will be evaluated. These studies should reveal if NLK is important in vivo for growth and survival of motor neurons and proprioceptive sensory neurons.
