Microtubule destabilization and neurofilament phosphorylation precede dendritic sprouting after close axotomy of lamprey central neurons.

Axotomy of giant lamprey (Petromyzon marinus) central neurons (anterior bulbar cells) close to their somata results in ectopic axon-like sprouting from the dendritic tips. Such sprouts first appear as swellings at the tips of a small subset of dendrites 2-3 weeks after "close" axotomy. We report here that immunocytochemical examination of these swellings reveals a structure and composition that differs from that of conventional growth cones; incipient sprouts contain many highly phosphorylated neurofilaments (NFs), little tubulin, and virtually no stable (acetylated) microtubules (MTs). The dendrites of anterior bulbar cells after close axotomy also show pronounced changes in NF protein and tubulin staining patterns prior to the emergence of sprouts from the dendrites. The amount of tyrosinated tubulin increases greatly; this rise is tightly coupled to the appearance of highly phosphorylated NFs and the loss of nonphosphorylated NFs in the dendrites. Acetylated tubulin is generally reduced after close axotomy and is selectively lost from dendrites that gave rise to sprouts. These changes indicate that an invasion of the dendrites by phosphorylated NFs may be linked to the destabilization of dendritic MTs, and in some dendrites this may lead to a marked loss of stable MTs, which is correlated with the emergence of NF-filled sprouts from the dendritic tips.