title: Inhibition of cell proliferation does not slow down echinoderm neural regeneration.
abstract: BACKGROUND
  Regeneration of the damaged central nervous system is one of the most interesting post-embryonic developmental phenomena. Two distinct cellular events have been implicated in supplying regenerative neurogenesis with cellular material - generation of new cells through cell proliferation and recruitment of already existing cells through cell migration. The relative contribution and importance of these two mechanisms is often unknown.
  
  
  METHODS
  Here, we use the regenerating radial nerve cord (RNC) of the echinodermHolothuria glaberrimaas a model of extensive post-traumatic neurogenesis in the deuterostome central nervous system. To uncouple the effects of cell proliferation from those of cell migration, we treated regenerating animals with aphidicolin, a specific inhibitor of S-phase DNA replication. To monitor the effect of aphidicolin on DNA synthesis, we used BrdU immunocytochemistry. The specific radial glial marker ERG1 was used to label the regenerating RNC. Cell migration was tracked with vital staining with the lipophilic dye DiI.
  
  
  RESULTS
  Aphidicolin treatment resulted in a significant 2.1-fold decrease in cell proliferation. In spite of this, the regenerating RNC in the treated animals did not differ in histological architecture, size and cell number from its counterpart in the control vehicle-treated animals. DiI labeling showed extensive cell migration in the RNC. Some cells migrated from as far as 2 mm away from the injury plane to contribute to the neural outgrowth.
  
  
  CONCLUSIONS
  We suggest that inhibition of cell division in the regenerating RNC ofH. glaberrimais compensated for by recruitment of cells, which migrate into the RNC outgrowth from deeper regions of the neuroepithelium. Neural regeneration in echinoderms is thus a highly regulative developmental phenomenon, in which the size of the cell pool can be controlled either by cell proliferation or cell migration, and the latter can neutralize perturbations in the former.
authors.affiliation: University of North Florida, 1 UNF Drive, Jacksonville, 32224 FL USA.|University of Puerto Rico, Rio Piedras, PO Box 70377, San Juan, 00936-8377 PR USA.
authors.forename: Vladimir S
authors.identifier: 0000-0001-6875-7518
authors.initials: VS
authors.lastname: Mashanov
authors.affiliation: University of North Florida, 1 UNF Drive, Jacksonville, 32224 FL USA.|University of Puerto Rico, Rio Piedras, PO Box 70377, San Juan, 00936-8377 PR USA.
authors.forename: Olga R
authors.initials: OR
authors.lastname: Zueva
authors.affiliation: University of Puerto Rico, Rio Piedras, PO Box 70377, San Juan, 00936-8377 PR USA.
authors.forename: José E
authors.initials: JE
authors.lastname: García-Arrarás
keywords: Cell division; Cell migration; Central nervous system; Echinoderm; Neurogenesis; Regeneration