The proposed research is aimed at investigating the mechanisms that control the formation of neuronal networks during brain development. The research will be focused on the role that membrane components of the nerve growth cone play in these mechanisms. Of particular interest are: (i) the kinetics of specific plasmalemmal components of the neuron during growth, (ii) the biochemical nature of growth cone membrane constituents and their variation when growth cones from different types of neuron are compared, and (iii) the changes in membrane components of the growth cone induced by target cell recognition and synaptogenesis. The proposed experiments include cytochemical studies with monoclonal antibodies on neurons grown in culture, subcellular fractionation of nerve growth cones and biochemical analysis of their membrane components, immunochemical comparison of nerve growth cones and presynaptic endings, and cytochemical studies on axons interacting with targets in vitro under various experimental conditions. This work is expected to lead to new insights into the molecular mechanisms of cell-cell recognition in the nervous system and synaptogenesis. It will thus eventually be crucial to investigations on the causes of developmental disorders of the nervous system.
| Pfenninger, K H (1987) Plasmalemmal properties of the sprouting neuron. Curr Top Dev Biol 21:185-206 |
| Meiri, K F; Pfenninger, K H; Willard, M B (1986) Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci U S A 83:3537-41 |
| Greenberger, L M; Pfenninger, K H (1986) Membrane glycoproteins of the nerve growth cone: diversity and growth regulation of oligosaccharides. J Cell Biol 103:1369-82 |
