Division of Biological Science, Graduate School of Science, Nagoya University, Furo, Chikusa, Nagoya, Aichi, 464-8602, Japan.
Division of Biological Science, Graduate School of Science, Nagoya University, Furo, Chikusa, Nagoya, Aichi, 464-8602, Japan; Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan.
Dev Biol. 2019 Nov 15;455(2):393-408. doi: 10.1016/j.ydbio.2019.07.010. Epub 2019 Jul 16.
The cerebellum and the cerebellum-like structure in the mesencephalic tectum in zebrafish contain multiple cell types, including principal cells (i.e., Purkinje cells and type I neurons) and granule cells, that form neural circuits in which the principal cells receive and integrate inputs from granule cells and other neurons. It is largely unknown how these cells are positioned and how neural circuits form. While Reelin signaling is known to play an important role in cell positioning in the mammalian brain, its role in the formation of other vertebrate brains remains elusive. Here we found that zebrafish with mutations in Reelin or in the Reelin-signaling molecules Vldlr or Dab1a exhibited ectopic Purkinje cells, eurydendroid cells (projection neurons), and Bergmann glial cells in the cerebellum, and ectopic type I neurons in the tectum. The ectopic Purkinje cells and type I neurons received aberrant afferent fibers in these mutants. In wild-type zebrafish, reelin transcripts were detected in the internal granule cell layer, while Reelin protein was localized to the superficial layer of the cerebellum and the tectum. Laser ablation of the granule cell axons perturbed the localization of Reelin, and the mutation of both kif5aa and kif5ba, which encode major kinesin I components in the granule cells, disrupted the elongation of granule cell axons and the Reelin distribution. Our findings suggest that in zebrafish, (1) Reelin is transported from the granule cell soma to the superficial layer by axonal transport; (2) Reelin controls the migration of neurons and glial cells from the ventricular zone; and (3) Purkinje cells and type I neurons attract afferent axons during the formation of the cerebellum and the cerebellum-like structure.
小脑和中脑脑桥被盖中的小脑样结构包含多种细胞类型，包括主细胞（即浦肯野细胞和 I 型神经元）和颗粒细胞，它们形成神经回路，其中主细胞接收和整合来自颗粒细胞和其他神经元的输入。这些细胞如何定位以及神经回路如何形成在很大程度上是未知的。虽然 Reelin 信号在哺乳动物大脑中的细胞定位中起着重要作用，但它在其他脊椎动物大脑形成中的作用仍不清楚。在这里，我们发现 Reelin 或 Reelin 信号分子 Vldlr 或 Dab1a 突变的斑马鱼在小脑中有异位浦肯野细胞、 eurydendroid 细胞（投射神经元）和 Bergmann 胶质细胞，在脑桥中有异位 I 型神经元。这些突变体中的异位浦肯野细胞和 I 型神经元接收异常传入纤维。在野生型斑马鱼中，reelin 转录本在内部颗粒细胞层中被检测到，而 Reelin 蛋白定位于小脑和脑桥的浅层。颗粒细胞轴突的激光消融扰乱了 Reelin 的定位，而 kif5aa 和 kif5ba 的突变，这两个基因编码颗粒细胞中的主要驱动蛋白 I 成分，破坏了颗粒细胞轴突的伸长和 Reelin 的分布。我们的研究结果表明，在斑马鱼中，（1）Reelin 由轴突运输从颗粒细胞体运输到浅层；（2）Reelin 控制神经元和神经胶质细胞从脑室区的迁移；（3）浦肯野细胞和 I 型神经元在小脑和小脑样结构的形成过程中吸引传入轴突。
