A central unsolved problem in neurobiology is how selective patterns of neuronal projections are established in development. One important clue to understanding regulation of this process is that different stages are associated with qualitatively distinct modes of growth. Growth to targets is characterized by relatively rapid advancement along stereotyped routes with extensive fasciculation and minimal branching, while innervation of target involves slower growth and multiple branching associated with extensive remodelling (arborization mode). The proposed research seeks to elucidate characteristic axonal interactions with their environment which may be critical for the differential growth patterns in the two stages. Electron microscopic analysis of growing optic axons will concentrate on determining whether the first fibers elongate as fascicles or as individual pioneer fibers and whether they consistently associate with processes of radial glial cells and extracellular matrix materials to their targets. Studies in the superior colliculus will provide comparative analysis of the associations of axonal processes in the early stages of arborization. These studies will provide a foundation for immunocytochemical investigations of the expression of antigens which are candidates for agents which may implement axon-environmental interactions characteristic of particular modes of growth. We will focus on the relationship of two antigens (a ganglioside and a glycoprotein) with the elongation mode. Finally, cellular events associated with the arborization mode in the colliculus will be examined through the use of anterograde and retrograde tracer substances. Causal interrelationships among the following temporally overlapping events will be investigated in postnatal development: improvements in retinotopic organization of the projection, reshaping of optic arbors, retinal ganglion cell death, and massive elimination of a system of superficial fiber bundles. This research will advance our knowledge of the cellular and molecular controls on axonal growth patterns, a necessary prerequisite before we can devise interventions which can improve recovery of function after brain damage.
