Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Development. 2023 Sep 15;150(18). doi: 10.1242/dev.201666.
Glia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal features of pro-regenerative glia that could be exploited for new human therapies. Planarian flatworms completely regenerate their nervous systems after injury - including glia - and thus provide a strong model system for exploring glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons, and that neurons are required for correct glial numbers and localization during regeneration. We also identify the planarian transcription factor-encoding gene ets-1 as a key regulator of glial cell maintenance and regeneration. Using ets-1 (RNAi) to perturb glia, we show that glial loss is associated with altered neuronal gene expression, impeded animal movement and impaired nervous system architecture - particularly within the neuropil. Importantly, our work reveals the inter-relationships of glia and neurons in the context of robust neural regeneration.
神经胶质在应对损伤时发挥多方面的作用。根据物种、损伤程度和所涉及的神经胶质细胞类型,神经胶质可以帮助或阻碍神经元的再生。在成功再生的背景下研究神经胶质,可以揭示出有利于神经再生的神经胶质的特征,这些特征可以为新的人类治疗方法提供依据。涡虫在受伤后可以完全再生其神经系统,包括神经胶质,因此为探索再生背景下的神经胶质提供了一个强有力的模型系统。在这里,我们报告说,神经元再生后,神经胶质也会再生,并且神经元对于再生过程中神经胶质数量和定位的正确是必需的。我们还确定了涡虫转录因子编码基因 ets-1 是神经胶质细胞维持和再生的关键调节因子。通过使用 ets-1(RNAi)来干扰神经胶质,我们表明神经胶质的丧失与神经元基因表达的改变、动物运动能力的受损以及神经系统结构的损伤有关,尤其是神经突内。重要的是,我们的工作揭示了在强大的神经再生背景下神经胶质和神经元之间的相互关系。