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.

Highlights

  • 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

  • We take an advantage of recently generated monoclonal antibodies [22] to provide the first comprehensive analysis of the role of radial glial cells in CNS regeneration in echinoderms. We show that both glia and neurons undergo programmed cell death in response to injury, but it is the radial glia that take the leading role in subsequent regeneration by making up the leading tip of the growing regenerate, producing new cells through cell division and giving rise to new neurons

  • Organization of the uninjured radial nerve Here, we provide a brief background on the organization of the sea cucumber central nervous system

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Summary

Introduction

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. It is accepted that the central nervous system (CNS) can continue producing new cells after an animal reaches adulthood. Adult neurogenesis results in production of new cells to support certain behaviors, sensory functions, or continuous lifelong body growth under normal physiological conditions, and involves the ability to regenerate lesioned CNS regions. There have been a growing number of studies of neural regeneration in regeneration-competent non-mammalian vertebrates aimed at getting insight into if and how regenerative response in the human nervous system can be improved

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