Abstract

A critical step in regeneration of a transected axon is the transformation of the cut axonal end into a motile growth cone (GC) which orchestrates in time and space the use of cell resources for growth processes. Using live confocal imaging complemented by electron microscopy, immunolabeling, electrophysiological methods and cultured Aplysia neurons we analyzed the mechanisms by which axotomy activates local self-assembly processes that transform a cut axonal end into a competent GC. In my presentation I will (a) describe the cascades that orchestrate the transformation of a differentiated axon into a motile growth cone after axotomy. The description will include the following parameters: axotomy-induced calcium concentration gradients, membrane seal formation, calpain activation, restructuring of the cytoskeleton (microtubules, actin and spectrin), the formation of “traps” that capture and sort vesicles and mitochondria, and fusion of vesicles with the GC’s plasma membrane in support of the growth process. (b) Analyze experimental results that relate improper restructuring of cytoskeletal elements at the cut axonal end to the failure to assemble competent GCs by neurons with high capacity to regenerate. And finally©, present potential approaches to overcome the subcellular barriers that impede regrowth from incompetent GCs – endbulbs.