Oligodendrocytes produce multi-lamellar myelin membranes that surround axons in the central nervous system (CNS). Preservation and generation of myelin are potential therapeutic targets for dysmyelinating and demyelinating diseases. MicroRNAs (miRNAs) play a vital role in oligodendrocyte differentiation and overall CNS development. miR-124 is a well-conserved neuronal miRNA with important roles in neuronal differentiation and function. miR-124 levels increase following loss of myelin in both human and rodent brains. While the role of neuronal miR-124 in neurogenesis has been established, its effects on axonal outgrowth and oligodendrocytes are not currently known. We therefore explored the possible effect of selective knockdown of miR-124 in Danio rerio using a morpholino-based knockdown approach. No morphological abnormalities or loss of motor neurons were detected despite loss of axonal outgrowth. Morpholino-based knockdown of miR-124 led to reciprocal increases in mRNA levels of target genes that inhibit axonal and dendritic projections. Importantly, loss of miR-124 led to decreased oligodendrocyte cell numbers and myelination of axonal projections in the ventral hindbrain. Taken together, our results add a new dimension to the existing complexity of neuron–glial relationships and highlight the utility of Danio rerio as a model system to investigate such interactions.

中文翻译：

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进化保守的microRNA miR-124的水平降低会影响斑马鱼（Danio rerio）的少突胶质细胞数量。

少突胶质细胞产生围绕中枢神经系统（CNS）轴突的多层髓鞘膜。髓鞘蛋白的保存和生成是使髓鞘异常和脱髓鞘疾病的潜在治疗靶标。MicroRNA（miRNA）在少突胶质细胞分化和整个CNS发育中起着至关重要的作用。miR-124是一个保存良好的神经元miRNA，在神经元分化和功能中具有重要作用。人和啮齿动物大脑中的髓磷脂丧失后，miR-124水平升高。虽然已经确定了神经元miR-124在神经发生中的作用，但目前尚不清楚其对轴突生长和少突胶质细胞的作用。因此，我们探讨了选择性敲低miR-124在Danio rerio中的可能作用。使用基于吗啉代的击倒方法。尽管轴突生长丧失，但未检测到形态异常或运动神经元丧失。基于Morpholino的miR-124敲低导致抑制轴突和树突状投射的靶基因mRNA水平上的相互增加。重要的是，miR-124的缺失导致少突胶质细胞的数量减少以及腹后脑轴突突起的髓鞘化。综上所述，我们的结果为神经元-神经胶质关系的现有复杂性增加了新的维度，并强调了Danio rerio作为研究此类相互作用的模型系统的实用性。