Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish
Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish
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DOI：
10.1016/j.expneurol.2013.11.012
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发表时间：
2014-01-01
影响因子：
5.3
通讯作者：
Hu, Bing
中科院分区：
文献类型：
--
作者：
Yin, Wu;Hu, Bing
脱髓鞘疾病包括多发性硬化症，这是一种神经退行性疾病，其特征是对中枢神经系统（CNS）的免疫攻击，导致髓鞘损伤和轴突损失。富含亮氨酸重复序列和含有免疫球蛋白结构域的神经突生长抑制蛋白 (Nogo) 受体相互作用蛋白 1 (LINGO-1) 已被确定为少突胶质细胞分化的负调节因子。靶向 LINGO-1 抑制可促进多种动物模型中的神经元存活、轴突再生、少突胶质细胞分化和髓鞘再生。尽管啮齿动物模型的研究扩展了我们对 LINGO-I 的理解，但其在斑马鱼 (Danio rerio) 神经发育和髓鞘形成中的作用尚不清楚。在这项研究中，我们克隆了人类 LINGO-1 的斑马鱼同源物，发现 lingo1b 调节髓鞘形成和少突胶质细胞分化。 lingo1b 在中枢神经系统受精后 (dpf) 1 天（mRNA）和 2 天（蛋白质）开始表达。吗啡寡核苷酸敲低 lingo1b 会导致发育异常，包括深色色素减少、眼睛小和脊髓卷曲。 lingo1b 的缺乏增强了胚胎发生过程中的髓鞘形成和少突胶质细胞的分化。此外，免疫组织化学和运动分析表明 lingo1b 参与初级运动神经元的轴突发育。这些结果表明，Lingo1b 蛋白在斑马鱼发育过程中充当髓鞘形成和少突胶质细胞分化的负调节因子 (C) 2013 Elsevier Inc. 保留所有权利。
Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-I, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development (C) 2013 Elsevier Inc. All rights reserved.