BACKGROUND In the peripheral nervous system (PNS), specialized glial cells called Schwann cells produce myelin, a lipid-rich insulating sheath that surrounds axons and promotes rapid action potential propagation. During development, Schwann cells must undergo extensive cytoskeletal rearrangements in order to become mature, myelinating Schwann cells. The intracellular mechanisms that drive Schwann cell development, myelination, and accompanying cell shape changes are poorly understood. METHODS Through a forward genetic screen in zebrafish, we identified a mutation in the atypical guanine nucleotide exchange factor, dock1, that results in decreased myelination of peripheral axons. Rescue experiments and complementation tests with newly engineered alleles confirmed that mutations in dock1 cause defects in myelination of the PNS. Whole mount in situ hybridization, transmission electron microscopy, and live imaging were used to fully define mutant phenotypes. RESULTS We show that Schwann cells in dock1 mutants can appropriately migrate and are not decreased in number, but exhibit delayed radial sorting and decreased myelination during early stages of development. CONCLUSIONS Together, our results demonstrate that mutations in dock1 result in defects in Schwann cell development and myelination. Specifically, loss of dock1 delays radial sorting and myelination of peripheral axons in zebrafish.

中文翻译：

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Dock1中的突变破坏了早期Schwann细胞的发育。

背景技术在周围神经系统（PNS）中，称为雪旺氏细胞的专门神经胶质细胞产生髓磷脂，髓磷脂是富含脂质的绝缘鞘，围绕轴突并促进动作电位的快速传播。在发育过程中，雪旺氏细胞必须经历广泛的细胞骨架重排才能成为成熟的髓鞘雪旺氏细胞。人们对驱动雪旺氏细胞发育，髓鞘形成和伴随的细胞形状改变的细胞内机制了解甚少。方法通过对斑马鱼进行前向遗传筛选，我们发现了非典型鸟嘌呤核苷酸交换因子dock1的突变，该突变导致外周轴突的髓鞘减少。使用新设计的等位基因进行的抢救实验和补充测试证实，dock1中的突变导致PNS髓鞘形成缺陷。整个安装原位杂交，透射电子显微镜和实时成像被用来完全定义突变体表型。结果我们显示，dock1突变体中的Schwann细胞可以适当迁移并且数量没有减少，但是在发育的早期阶段显示出延迟的径向分选和髓鞘减少。结论在一起，我们的结果表明，dock1中的突变导致雪旺氏细胞发育和髓鞘形成的缺陷。具体来说，dock1的丢失会延迟斑马鱼的径向分类和外周轴突的髓鞘形成。但在发育的早期阶段会出现放射状分选延迟和髓鞘减少的现象。结论在一起，我们的结果表明，dock1中的突变导致雪旺氏细胞发育和髓鞘形成的缺陷。具体来说，dock1的丢失会延迟斑马鱼的径向分类和外周轴突的髓鞘形成。但在发育的早期阶段会出现放射状分选延迟和髓鞘减少的现象。结论在一起，我们的结果表明，dock1中的突变会导致雪旺氏细胞发育和髓鞘形成的缺陷。具体来说，dock1的丢失会延迟斑马鱼的径向分类和外周轴突的髓鞘形成。