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

神经干细胞存在于成体中枢神经系统中，但哺乳动物中枢神经系统不进行大规模再生，可能是因为发育过程中存在的环境线索不存在于成体中。一个主要的挑战是诱导这些干细胞取代受损的中枢神经系统。蝾螈等尾纲两栖动物是解决这一问题的一个模型，因为脊髓再生涉及所有神经细胞类型的再生，发生在尾巴截肢后。受伤的尾索组织产生一个胚胎生长区，能够形成一条完美的尾巴。关于生长区是如何建立的，以及生长区中诱导神经干细胞进行增殖和成型化的信号，我们知之甚少。为了解决这些问题，我们将使用高分辨率的细胞谱系追踪来首先定义神经干细胞的来源，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，以确定蝾螈组织是否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断了蝾螈的反应。

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.