Systems Biology Group (SysBio), Institute of Physics of Liquids and Biological Systems (IFLySIB), National Scientific and Technical Research Council (CONICET) and University of La Plata (UNLP), La Plata, Argentina.
The Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Elife. 2021 May 14;10:e55665. doi: 10.7554/eLife.55665.
Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modeling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830 μm of the injury. We adapted Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding spinal cord regeneration.
蝾螈具有独特的解决脊髓损伤的能力，但对脊髓再生的机制知之甚少。我们之前发现，尾巴截肢会导致脊髓室管膜细胞重新激活一种类似于发育的程序（Rodrigo Albors 等人，2015 年），其特征是在截肢后 4 天出现高增殖区（Rost 等人，2016 年）。然而，这种细胞增殖的时空模式的基础仍然未知。在这里，我们使用与实验数据紧密结合的建模来证明，这种再生反应与一种信号一致，该信号在截肢后约 85 小时内、损伤处约 830 μm 范围内招募室管膜细胞。我们将荧光泛素化细胞周期指示剂 (FUCCI) 技术改编为蝾螈 (AxFUCCI)，以在体内可视化细胞周期。AxFUCCI 蝾螈证实了预测的损伤诱导募集区的出现时间和大小，并揭示了室管膜细胞之间的细胞周期同步性。我们的建模和成像使我们更接近于理解脊髓再生。
