Graduate School of Life Science, University of Hyogo, Ako-gun, Hyogo 678-1297, Japan.
School of Science, University of Hyogo, Ako-gun, Hyogo 678-1297, Japan.
Development. 2021 Jan 26;148(2):dev195339. doi: 10.1242/dev.195339.
The enteric nervous system (ENS), which is derived from neural crest, is essential for gut function, and its deficiency causes severe congenital diseases. Since the capacity for ENS regeneration in mammals is limited, additional complementary models would be useful. Here, we show that the ENS in zebrafish larvae at 10-15 days postfertilization is highly regenerative. After laser ablation, the number of enteric neurons recovered to ∼50% of the control by 10 days post-ablation (dpa). Using transgenic lines in which enteric neural crest-derived cells (ENCDCs) and enteric neurons are labeled with fluorescent proteins, we live imaged the regeneration process and found covering by neurites that extended from the unablated area and entry of ENCDCs into the ablated areas by 1-3 dpa. BrdU assays suggested that ∼80% of the enteric neurons and ∼90% of the Sox10-positive ENCDCs therein at 7 dpa were generated through proliferation. Thus, ENS regeneration involves proliferation, entrance and neurogenesis of ENCDCs. This is the first report regarding the regeneration process of the zebrafish ENS. Our findings provide a basis for further research at single-cell resolution in this vertebrate model.
肠神经系统（ENS）源自神经嵴，对肠道功能至关重要，其缺乏会导致严重的先天性疾病。由于哺乳动物 ENS 的再生能力有限，因此额外的补充模型将是有用的。在这里，我们展示了在受精后 10-15 天的斑马鱼幼虫中，ENS 具有高度的再生能力。在激光消融后，到消融后 10 天（dpa）时，肠神经元的数量恢复到对照组的约 50%。使用荧光蛋白标记肠神经嵴衍生细胞（ENCDCs）和肠神经元的转基因系，我们对再生过程进行了活体成像，发现到 1-3 dpa 时，从未消融区域延伸出的神经突覆盖和 ENCDCs 进入消融区域。BrdU 测定表明，到 7 dpa 时，大约 80%的肠神经元和约 90%的 Sox10 阳性 ENCDCs 是通过增殖产生的。因此，ENS 再生涉及增殖、ENCDCs 的进入和神经发生。这是关于斑马鱼 ENS 再生过程的第一个报道。我们的研究结果为在这种脊椎动物模型中以单细胞分辨率进一步研究提供了基础。
