Radial glial cells play a key role in echinoderm neural regeneration

Abstract

BackgroundUnlike the mammalian central nervous system (CNS), the CNS of echinoderms is capable of fast and efficient regeneration following injury and constitutes one of the most promising model systems that can provide important insights into evolution of the cellular and molecular events involved in neural repair in deuterostomes. So far, the cellular mechanisms of neural regeneration in echinoderm remained obscure. In this study we show that radial glial cells are the main source of new cells in the regenerating radial nerve cord in these animals.ResultsWe demonstrate that radial glial cells of the sea cucumber Holothuria glaberrima react to injury by dedifferentiation. Both glia and neurons undergo programmed cell death in the lesioned CNS, but it is the dedifferentiated glial subpopulation in the vicinity of the injury that accounts for the vast majority of cell divisions. Glial outgrowth leads to formation of a tubular scaffold at the growing tip, which is later populated by neural elements. Most importantly, radial glial cells themselves give rise to new neurons. At least some of the newly produced neurons survive for more than 4 months and express neuronal markers typical of the mature echinoderm CNS.ConclusionsA hypothesis is formulated that CNS regeneration via activation of radial glial cells may represent a common capacity of the Deuterostomia, which is not invoked spontaneously in higher vertebrates, whose adult CNS does not retain radial glial cells. Potential implications for biomedical research aimed at finding the cure for human CNS injuries are discussed.

The complex simplicity of the brittle star nervous system

“…6). The brittle star radial glia is very similar to their counterparts previously described in starfish and sea cucumbers [12, 14, 17, 18]. These cells are robustly labeled by the ERG1 antibody (Figs.…”

“…Fluorescent immunohistochemistry on frozen sections was performed as described elsewhere [12]. Briefly, animals were anesthetized in 0.2% chlorobutanol (Sigma) and then portions of the arm, approximately 5 segments long, were fixed in 4% paraformaldehyde prepared in 0.01 M PBS (pH 7.4) overnight at 4 °C.…”

Echinodermata

“…Interestingly, it has been shown that in mammals, glial cells are also involved in the regenerative process, as in holothurians (and probably in all echinoderms), but, while in echinoderms the radial glia are active in the regeneration process (Mashanov et al 2013 ), in mammals glial cells become a factor that block the process (Shearer and Fawcett 2001 ). In early-branching vertebrates, the glial reaction is, instead, permissive of regeneration (Zukor et al 2011 ).…”

“…However, it is from the recent study of holothuroids that new insights have been gained (see Mashanov et al 2008Mashanov et al , 2013. After transection of the radial nerve cord (RNC) in Eupentacta fraudatrix , the RNC regenerates and reconnects in about 20 days.…”

“…Regeneration of other structures, such the holothurian nervous system, has also attracted much interest over the last few years (Mashanov et al 2008(Mashanov et al , 2013. Here, the current knowledge of echinoderm regenerative processes is summarized.…”