CYTOSKELETAL CHANGES CORRELATED WITH THE LOSS OF NEURONAL POLARITY INAXOTOMIZED LAMPREY CENTRAL NEURONS

Axotomy within 500 mu m of the soma (close axotomy) causes identified neurons (anterior bulbar cells or ABCs) in the lamprey hindbrain to lo se their normal polarity and regenerate axons ectopically from dendrit ic tips, while axotomy at more distal sites (distant axotomy) results in orthotopic axonal regeneration from the axon stump. We performed im munocytochemical, electron microscopic and in situ hybridization analy ses comparing ABCs subjected to close and distant axotomy to elucidate the mechanism by which neuronal polarity is lost. We show that polari ty loss in ABCs is selectively and invariably preceded and accompained by the following cellular changes: (1) a loss of many dendritic micro tubules and their replacement with neurofilaments, (2) a loss of immun ostaining for acetylated tubulin in the soma and proximal dendrites, a nd (3) an increase of immunostaining for phosphorylated neurofilaments in the distal dendrites. We also show that these changes do not depen d on either the upregulation or spatial redistribution of neurofilamen t message, and thus must involve changes in the routing of neurofilame nt protein within axotomized ABCs. We conclude that close axotomy caus es dendrites to undergo axonlike changes in the mechanisms that govern the somatofugal transport of neurofilament protein, and suggest that these changes require the reorganization of dendritic microtubules. We also suggest that the bulbous morphology and lack of f-actin in the t ips of all regenerating sprouts supports the possibility that axonal r egeneration in the lamprey CNS does not involve actin-mediated ''pulli ng'' of growth cones, but depends instead on the generation of interna l extrusive forces.