Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration.
Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration.
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DOI：
10.7554/elife.55665
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发表时间：
2021-05-14
期刊：
影响因子：
7.7
通讯作者：
Chara O
中科院分区：
文献类型：
--
作者：
Cura Costa E;Otsuki L;Rodrigo Albors A;Tanaka EM;Chara O
Axolotls是唯一能够解决脊髓损伤的药物，但对脊髓再生的机制知之甚少。我们先前发现，截尾导致脊髓室管膜细胞中发育样程序的重新激活(Rodrigo Albors等人，2015)，其特征是截尾后4天出现高增殖区(Rost等人，2016)。然而，这种细胞增殖的时空模式背后的原因尚不清楚。在这里，我们使用与实验数据紧密联系的建模来证明这种再生反应与在损伤后约85小时内在损伤约830μm内招募室管膜细胞的信号是一致的。我们将基于泛素化的荧光细胞周期指示器(Fucci)技术应用于Axolotls(AxFUCCI)，以可视化体内的细胞周期。AxFUCCI axolotls证实了损伤诱导的募集区的出现时间和大小的预测，并揭示了室管膜细胞之间的细胞周期同步。我们的建模和成像使我们更接近了解真正的脊髓再生。
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 bona fide spinal cord regeneration.