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.

BackgroundEchinoderms are emerging as important models in regenerative biology. Significant amount of data are available on cellular mechanisms of post-traumatic repair in these animals, whereas studies of gene expression are rare. In this study, we employ high-throughput sequencing to analyze the transcriptome of the normal and regenerating radial nerve cord (a homolog of the chordate neural tube), in the sea cucumber Holothuria glaberrima.ResultsOur de novo assembly yielded 70,173 contigs, of which 24,324 showed significant similarity to known protein-coding sequences. Expression profiling revealed large-scale changes in gene expression (4,023 and 3,257 up-regulated and down-regulated transcripts, respectively) associated with regeneration. Functional analysis of sets of differentially expressed genes suggested that among the most extensively over-represented pathways were those involved in the extracellular matrix (ECM) remodeling and ECM-cell interactions, indicating a key role of the ECM in regeneration. We also searched the sea cucumber transcriptome for homologs of factors known to be involved in acquisition and/or control of pluripotency. We identified eleven genes that were expressed both in the normal and regenerating tissues. Of these, only Myc was present at significantly higher levels in regeneration, whereas the expression of Bmi-1 was significantly reduced. We also sought to get insight into which transcription factors may operate at the top of the regulatory hierarchy to control gene expression in regeneration. Our analysis yielded eleven putative transcription factors, which constitute good candidates for further functional studies. The identified candidate transcription factors included not only known regeneration-related genes, but also factors not previously implicated as regulators of post-traumatic tissue regrowth. Functional annotation also suggested that one of the possible adaptations contributing to fast and efficient neural regeneration in echinoderms may be related to suppression of excitotoxicity.ConclusionsOur transcriptomic analysis corroborates existing data on cellular mechanisms implicated in regeneration in sea cucumbers. More importantly, however, it also illuminates new aspects of echinoderm regeneration, which have been scarcely studied or overlooked altogether. The most significant outcome of the present work is that it lays out a roadmap for future studies of regulatory mechanisms by providing a list of key candidate genes for functional analysis.

The nervous system of echinoderms has long been considered too unique to be directly comparable to the nervous system of other Deuterostomia. Using two novel monoclonal antibodies in combination with epifluorescence, confocal, and electron microscopy, we demonstrate here that the central nervous system of the sea cucumber Holothuria glaberrima possesses a major non-neuronal cell type, which shares striking similarities with the radial glia of chordates. The basic features in common include (a) an elongated shape, (b) long radial processes, (c) short lateral protrusions branching off the main processes and penetrating into the surrounding neuropile, (d) prominent orderly oriented bundles of intermediate filaments, and (e) ability to produce Reissner's substance. Radial glia account for the majority of glia cells in echinoderms and constitutes more than half of the total cell population in the radial nerve cord and about 45% in the circumoral nerve ring. The difference in glia cell number between those regions is significant, suggesting structural specialization within the seemingly simple echinoderm nervous system. Both cell death and proliferation are seen under normal physiological conditions. Although both glia and neurons undergo apoptosis, most of the mitotic cells are identified as radial glia, indicating a key role of this cell type in cell turnover in the nervous system. A hypothesis is proposed that the radial glia could be an ancestral feature of the deuterostome nervous system, and the origin of this cell type might have predated the diversification of the Chordata and Ambulacraria lineages.

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