Balancing degeneration and regeneration in the echinoderm nervous system

摘要 包括人类在内的成年哺乳动物的中枢神经系统再生能力， 是非常有限的这就是为什么在受伤或神经退行性疾病后， 在它们的余生中损害生物体。与哺乳动物相比，其他动物 不同程度的再生能力在后口动物中，棘皮动物以 它们惊人的修复和再生机制。这个建议使用棘皮动物，作为 新的模型系统，研究神经系统再生。这种生物，海参 Holothuria glaberrima具有天然的能力，可以再生其中央神经元的成分， 神经系统损伤或自残。 本提案旨在确定三种细胞机制（细胞 去分化、细胞增殖和细胞死亡）在变性和 再生将使用药理学和分子工具分析细胞机制。 实验策略利用了最近建立的神经细胞培养系统， 系统外植体和通过电穿孔触发去分化的能力。额外 实验的目的是确定神经系统的潜在分子基础 再生正常和再生神经成分的基因表达谱将 比较并用于鉴定与神经系统过程相关的基因 再生 我们的研究结果可以作为开发新疗法/药物的基础， 调节再生过程。它们还将为其他领域提供重要信息， 研究，包括伤口愈合，免疫学，细胞生物学，基因组学和生物遗传学。 最后，这些实验的结果将使我们更接近于更好地理解 一般来说，再生过程。

Abstract The capacity to regenerate the central nervous system of adult mammals, including humans, is highly limited. This is why loss of functions, following injuries or neurodegenerative diseases, impair the organisms for the rest of their life. In contrast to mammals, other animals have various degrees of regenerative abilities. Among deuterostomes, echinoderms are known for their amazing repair and regeneration mechanisms. This proposal uses an echinoderm, as a novel model system, to study nervous system regeneration. This organism, the sea cucumber Holothuria glaberrima, possesses the innate ability to regenerate components of its central nervous system following injury or autotomy. The present proposal searches to establish the role that three cellular mechanisms (cell dedifferentiation, cell proliferation and cell death) play in the balance between degeneration and regeneration. Cellular mechanisms will be analyzed using pharmacological and molecular tools. The experimental strategy takes advantage of a recently established culture system for nervous system explants and on the ability to trigger dedifferentiation by electroporation. Additional experiments are aimed at identifying the underlying molecular bases of nervous system regeneration. The gene expression profile of normal and regenerating nervous components will be compared and used to identify the genes associated with the process of nervous system regeneration. Our results could serve as the basis for the development of new therapeutics/drugs that modulate regenerative processes. They will also provide important information to other fields of research, including wound healing, immunology, cell biology, genomics and phylogenetics. Finally, the outcome of these experiments will bring us closer to a better understanding of regenerative processes in general.