Dynamic Changes in Ultrastructure of the Primary Cilium in Migrating Neuroblasts in the Postnatal Brain
Dynamic Changes in Ultrastructure of the Primary Cilium in Migrating Neuroblasts in the Postnatal Brain
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DOI：
10.1523/jneurosci.1503-19.2019
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发表时间：
2019-12-11
影响因子：
5.3
通讯作者：
Sawamoto, Kazunobu
中科院分区：
文献类型：
--
作者：
Matsumoto, Mami;Sawada, Masato;Sawamoto, Kazunobu
新的神经元，被称为神经母细胞，在动物的一生中不断地在脑室-脑室下区产生。这些神经母细胞的特点是其独特的增殖潜力，形成链状细胞聚集体，并通过吻侧迁移流（RMS）向嗅球（OB）长距离和高速迁移，在那里它们减速并分化为成熟的中间神经元。出生后神经母细胞在迁移过程中超微结构特征的动态变化尚不完全清楚。本研究报告了出生后RMS和OB中迁移的神经母细胞中存在初级纤毛，其超微结构形态和时空动力学。在雄性和雌性小鼠、斑马鱼和雄性恒河猴的出生后RMS和OB中迁移的神经母细胞中观察到初级纤毛。在神经母细胞迁移过程中，鞭毛内运输分子的抑制会损害它们的纤毛发生和向OB的吻侧迁移。连续切片透射电镜显示，每个迁移的神经母细胞都有一对中心粒或一个具有未成熟或成熟初级纤毛的基体。利用免疫组织化学、实时成像和连续块面扫描电镜，我们证明了初级纤毛的定位和方向取决于神经母细胞的有丝分裂状态、跳跃迁移和减速。总之，我们的研究结果强调了初级纤毛的时空调节与出生后大脑中神经母细胞的有效连锁迁移之间的密切相互关系。
New neurons, referred to as neuroblasts, are continuously generated in the ventricular-subventricular zone of the brain throughout an animal's life. These neuroblasts are characterized by their unique potential for proliferation, formation of chain-like cell aggregates, and long-distance and high-speed migration through the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they decelerate and differentiate into mature interneurons. The dynamic changes of ultrastructural features in postnatal-born neuroblasts during migration are not yet fully understood. Here we report the presence of a primary cilium, and its ultrastructural morphology and spatiotemporal dynamics, in migrating neuroblasts in the postnatal RMS and OB. The primary cilium was observed in migrating neuroblasts in the postnatal RMS and OB in male and female mice and zebrafish, and a male rhesus monkey. Inhibition of intraflagellar transport molecules in migrating neuroblasts impaired their ciliogenesis and rostral migration toward the OB. Serial section transmission electron microscopy revealed that each migrating neuroblast possesses either a pair of centrioles or a basal body with an immature or mature primary cilium. Using immunohistochemistry, live imaging, and serial block-face scanning electron microscopy, we demonstrate that the localization and orientation of the primary cilium are altered depending on the mitotic state, saltatory migration, and deceleration of neuroblasts. Together, our results highlight a close mutual relationship between spatiotemporal regulation of the primary cilium and efficient chain migration of neuroblasts in the postnatal brain.