The long-term goal of my research program is to examine the patterns and mechanisms involved in the establishment of longitudinal spinal pathways in the vertebrate using the relatively simple spinal cord of Xenopus laevis as a model. Questions of interest include: What are the mechanisms by which the basic neuronal pathways of the spinal cord are laid out? How do the axons of each of the many developing tracts decide which routes to follow to their targets? What kind of guidance cues might be involved and how do these differ for the multiple distinct tracts of the cord? How do axons of each behave when confronted with changes in their environment? Studies in our laboratory have already identified the earliest axon bundles of the spinal cord and have determined the sequence of their development. In addition, we have shown that growth cones navigating these pathways display quite variable behaviors which can be correlated with age, position in the pathway, and broadly defined neuron class. We now seek to define more precisely the growth patterns for specific spinal tracts. The experiments proposed here will pursue three main lines of investigation: 1) The behavior of growth cones as they navigate specific spinal pathways will be examined in wholemount preparations. These pathways will be identified using retrograde tracers and immunocytochemical markers. 2) Next, the substrate and contact relationships of identified growth cones along their pathway will be ascertained, and 3) The outgrowth patterns and directional choices made by growth cones of certain of these pathways will be tested as they encounter spinal segments of reversed rostrocaudal polarity. The results of these experiments will enhance our understanding of how the growth patterns of individual spinal pathways contribute to the achievement of spinal cord architecture. They will also help identify possible cues involved in pathfinding by specific axon groups, and will tell us something about the navigational capacities of neurons of specific tracts when confronted with an altered environment. All of the above issues are important considerations in the development of strategies for dealing with spinal cord defects and regeneration.
