The cellular and molecular analysis of amphibian spinal cord regeneration, and the comparison with mammalian cells

两栖动物脊髓再生的细胞和分子分析，以及与哺乳动物细胞的比较

• 批准号: 5304574
• 负责人: Professorin Dr. Elly Margaret Tanaka, Ph.D.
• 金额: --
• 依托单位: IMBA - Institute of Molecular Biotechnology GmbH
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2001
• 资助国家: 德国
• 起止时间: 2000-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5304574?language=en
• 关键词: cellular; molecular; analysis; amphibian; spinal

Neural stem cells reside in the adult central nervous system, yet the mammalian CNS does not undergo large-scale regeneration probably because the environmental cue present during development are not present in the adult. A major challenge is to induce these stem cells to replace damaged CNS. The urodele amphibian such as the axolotl represents a model to address this issue since spinal cord regeneration involving renewed neurogenesis of all neural cell types occurs after tail amputation. The injured urodele tissue produces an embryonic growth zone capable of reforming a perfect tail. Little is known about how the growth zone is established and the signals in the growth zone that induce the neural stem cells to undergo proliferation and patterning. To address these issues we will use high resolution cell lineage tracing to first define the source of the neural stem cells, how they are recruited to the injury site, and their fate. Second, we will use co-culture assays to determine the source and identity of the key signalling cues that direct neural stem cell proliferation and patterning. Finally, we will co-culture axolotl and mammalian CNS tissue to determine whether axolotl tissue stimulates mammalian stem cells and/or whether mammalian CNS tissue blocks the axolotl response.

神经干细胞存在于成体中枢神经系统中，但哺乳动物的中枢神经系统不经历大规模的再生，可能是因为发育过程中存在的环境提示在成体中不存在。一个主要的挑战是诱导这些干细胞来替代受损的CNS。有尾目两栖动物，如美西蝾螈代表了一个模型，以解决这个问题，因为脊髓再生涉及所有神经细胞类型的更新后发生断尾。受伤的有尾目动物组织产生一个胚胎生长区，能够重新形成一个完美的尾巴。人们对生长区如何建立以及生长区中诱导神经干细胞进行增殖和图案化的信号知之甚少。为了解决这些问题，我们将使用高分辨率细胞谱系追踪来首先确定神经干细胞的来源，它们如何被招募到损伤部位以及它们的命运。其次，我们将使用共培养试验来确定指导神经干细胞增殖和模式化的关键信号线索的来源和身份。最后，我们将共同培养蝾螈和哺乳动物中枢神经系统组织，以确定是否蝾螈组织刺激哺乳动物干细胞和/或哺乳动物中枢神经系统组织是否阻止蝾螈的反应。