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      Radial glial cells play a key role in echinoderm neural regeneration

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          Abstract

          Background

          Unlike 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.

          Results

          We 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.

          Conclusions

          A 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.

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          Most cited references38

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          Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain.

          Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP(+) cells does so, prompting the question of whether the proliferating GFAP(+) cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP(+) cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the platelet-derived growth factor (PDGFRalpha) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.
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            Molecular phylogeny and divergence times of deuterostome animals.

            The phylogenetic relationships among deuterostome animals have been debated for many years, and a diversity of hypotheses have been proposed based on both morphological and molecular data. Here we have assembled sequences of 217 nuclear-encoded proteins to address specific questions concerning their relationships and times of origin. We recovered significant support for urochordates as the closest relative of vertebrates with an analysis of 59 proteins (17,400 amino acids) and suggest that the basal position of urochordates found in previous molecular studies may have been the result of long-branch attraction biases. Our results also support Ambulacraria, the pairing of hemichordates with echinoderms (nine proteins; 2,382 amino acids), and Cyclostomata, the pairing of lampreys with hagfish (25 proteins; 6,895 amino acids). In addition, 325 shared proteins (102,110 amino acids) were obtained from the complete genomes of six vertebrates and a urochordate for phylogenetic analysis and divergence time estimation. An evolutionary timescale was estimated using a local (Bayesian) molecular clock method. We found that most major lineages of deuterostomes arose prior to the Cambrian Explosion of fossils (approximately 520 MYA) and that several lineages had originated before periods of global glaciation in the Precambrian.
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              Role of the lesion scar in the response to damage and repair of the central nervous system

              Traumatic damage to the central nervous system (CNS) destroys the blood–brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.
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                Author and article information

                Contributors
                Journal
                BMC Biol
                BMC Biol
                BMC Biology
                BioMed Central
                1741-7007
                2013
                18 April 2013
                : 11
                : 49
                Affiliations
                [1 ]Department of Biology, University of Puerto Rico, PO Box 70377, San Juan, PR, 00936-8377, USA
                Article
                1741-7007-11-49
                10.1186/1741-7007-11-49
                3652774
                23597108
                5fb6ea43-4fef-4a41-b4b5-1e8b441c2ea1
                Copyright © 2013 Mashanov et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 January 2013
                : 16 April 2013
                Categories
                Research Article

                Life sciences
                cellular mechanisms,central nervous system,echinodermata,injury,neurogenesis,radial glia,regeneration,sea cucumber

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