The structural role of radial glial endfeet in confining spinal motor neuron somata is controlled by the Reelin and Notch pathways
The structural role of radial glial endfeet in confining spinal motor neuron somata is controlled by the Reelin and Notch pathways
复制标题
放射状胶质末足在限制脊髓运动神经元体细胞中的结构作用由 Reelin 和 Notch 通路控制
DOI：
10.1016/j.expneurol.2013.08.010
复制
发表时间：
2013
影响因子：
5.3
通讯作者：
Mi
中科院分区：
文献类型：
--
作者：
Hojae Lee;Mi
神经元迁移是一个基本的生物学过程，它使神经元的精确定位形成功能电路。皮质神经元在Reelin配体的引导下沿着由放射状胶质形成的胶质支架迁移。然而，目前还不清楚放射状胶质细胞的Reelin定向行为是否也是定位脊髓神经元的关键。在这里，我们展示了一个新的作用，放射状胶质细胞，限制运动神经元内的神经管，并促进了Reelin和Notch信号。脊髓放射状胶质细胞表达Dab 1接头的Reelin信号转导和Reelin包围。在reelermice，其中Reelin是缺席的，异位运动神经元被发现的神经管外，虽然他们似乎保持自己的身份。边界帽（BC）细胞，雪旺细胞前体和在电机出口点的基底层是完整的，而放射状胶质细胞的胶质界是混乱的，从基底膜脱离。稀疏和不规则的放射状支架足够宽以允许运动胞体通过。Notch信号的强制激活挽救了小鼠放射状胶质细胞的结构缺陷和脊髓外神经元的出现。在不存在Reelin的情况下，Notch胞内结构域（NICD）蛋白水平降低。此外，通过破坏放射状胶质细胞支架的极性来破坏放射状胶质细胞支架可诱导鸡胚中的异位运动神经元。这些发现表明，需要通过Reelin激活Notch通路以建立放射状胶质支架，该支架是一种积极约束运动神经元胞体并指定CNS-PNS边界的结构。
Neuronal migration is a fundamental biological process that enables the precise positioning of neurons to form functional circuits. Cortical neurons migrate along glial scaffolds formed by radial glia guided by Reelin ligand. However, it is unclear whether the Reelin-directed behavior of radial glia is also critical for positioning the spinal neurons. Here we demonstrate a novel role of radial glia that confines motor neurons within the neural tube and is promoted by Reelin and Notch signaling. Spinal radial glia express the Dab1 adaptor for Reelin signaling and are surrounded by Reelin. Inreelermice, in which Reelin is absent, ectopic motor neurons are found outside the neural tube, although they appear to maintain their identity. Boundary cap (BC) cells, Schwann cell precursors and the basal lamina at motor exit points are intact, whereas the glia limitans of radial glia are disorganized and detached from the basement membrane. The sparse and irregular radial scaffold is wide enough to allow motor somata to pass. Forced activation of Notch signaling rescued the structural defects in radial glia inreelermice and the appearance of extraspinal neurons. In the absence of Reelin, Notch intracellular domain (NICD) protein level was reduced. In addition, disrupting the radial glia scaffold by destroying its polarity induced ectopic motor neurons in chick embryos. These findings suggest that activation of the Notch pathways by Reelin is required to establish the radial glial scaffold, a structure that actively constrains motor neuron somata and specifies the CNS–PNS boundary.