Dr. Bixby will examine the molecular basis of neuronal process growth by addressing two questions: First, what cell surface and extracellular matrix molecules act as growth and guidance cues for axons? Second, what are the intracellular (second messenger-related) events induced by these extracellular molecules that influence axonal growth? To answer the first question, a tissue culture system will be employed in which axons grow on sections of embryonic limb. Antibodies to extracellular matrix and cell surface adhesion molecules will be added to the cultures to determine which molecules specifically affect axonal growth. To answer the second question, neurons will be grown on artficial substrates consisting of certain purified substrate molecules. Axon growth will be assayed in the presence and absence of pharmacological agents that specifically affect the function of particular intracellular message systems. These experiments will provide evidence relating to the cascade of events stimulated by the binding of extracellular matrix and adhesion molecules to their neuronal receptors. The results will enhance knowledge of both the extrinsic regulatory molecules that influence growth during development, and the intracellular signaling systems triggered by these regulatory molecules.
