The principal aim of this proposal is to provide a complete structural analysis of ganglion cell growth cones and their contactss with other fibers and glial cells in the optic pathway of the fetal primate. No such analysis of growth cones exists yet in any species. This work is an essential prerequisite if we are to identify an understand the morphological substrates and ultimately, the molecular interactions that guide the growth of optic axons. The explicit objectives are to: 1. Compare and contrast the form and fine structure of growth cones in the nasal and temporal halves of retina, in the optic nerve, chiasm, and trast, and in target nuclei at several stages of development. The analysis will be based on 3- deimensioanla reconstructions from serial sections. 2. Characterize and quantify the local and global distribution growth cones in the optic pathway and their contact relations with different classes of glial and neuronal processes from the time when growth cones first enter the optic stalk through to the end of axon ingrowth. 3. Experimentally test the hypothesis that interactions between growth cones in the optic chiasm or optic tract regulate the development of the unique pattern of partial decussation that characterizes the primate visual system. Anterograde and retrograde tracer transport methods will be used to label specific populations of ganglion cells, their axons, and their growth cones. In recent studies I have identified and characterized growth cones in the optic nerve of the cat and monkey at the ultrastructural level, and I have demonstrated that growth cones are remarkabley variable in form, ultrastructure, and position. In collaboration with my colleagues, I developed new analytic techniques that now make possible a far more comprehensive study of growth cones The quantitative in situ analysis of growth cone should answer several outstanding questions, among them: How do the shape and ultrastructure of growth cones change in response to their environment? Are there structural differences between growth cones that have different destinations? How are the earliest pioneers in the optic pathway different from growth cones that follow? Do growth cones express an affinity for glial surfaces or basal lamina, and if so, do these preferences change with age or position? What interactions are there between growth cones and pre-existing axons that may help explain global patterns of axonal growth? How stable are these interactions and relations? Although fundamental, these issues have not been studied in any detail in any species and have not been studied at all in primates. The results of this work should have a direct bearing on several important hypotheses concerning the growth of axons and should result in new insights into the development of the visual system that will be of theoretical and clinical importance.
| Williams, R W; Rakic, P (1988) Elimination of neurons from the rhesus monkey's lateral geniculate nucleus during development. J Comp Neurol 272:424-36 |
| Williams, R W; Rakic, P (1988) Three-dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. J Comp Neurol 278:344-52 |
