Neurons tend to stop migration and differentiate along the cortical internal plexiform zones in the reelin signal-deficient mice
Neurons tend to stop migration and differentiate along the cortical internal plexiform zones in the reelin signal-deficient mice
复制标题
DOI：
10.1002/jnr.10345
复制
发表时间：
2002-09-15
影响因子：
4.2
通讯作者：
Nakajima, K
中科院分区：
文献类型：
--
作者：
Tabata, H;Nakajima, K
Reelin分子在皮质生成中起着重要作用。在Reelin与其受体结合后，Reelin信号通过细胞内适配蛋白失活1（Dab 1）的酪氨酸磷酸化转导。reelin基因缺陷的小鼠reeler和Dab 1基因缺陷的小鼠yotari显示神经元的定位被破坏。最近已确定了几种参与Reelin信号传导的分子，然而，Reelin在皮质板发育过程中的生物学功能仍然未知。我们观察了Reelin信号缺陷小鼠神经元在发育过程中的迁移行为。为了直接观察迁移的神经元，我们用子宫内电穿孔系统将绿色荧光蛋白（GFP）表达载体引入脑室区，并使胚胎在子宫内发育，直到进行分析。结果表明，突变体中的迁移细胞与正常小鼠的迁移细胞在形态上无明显区别。在正常小鼠中，当GFP表达细胞到达软脑膜表面附近的边缘区并开始树突形成时，在突变体皮层的各种更深位置发现GFP阳性细胞。它们具有迁移细胞的形态，向软膜表面延伸引导突起。相比之下，在突变体中，这些细胞倾向于沿着内丛状区的边界停止迁移，内丛状区是突变体皮层中主要由树突组成的不规则结构。出生后，这些神经元开始发育树突晚于正常皮质中的细胞。在此过程中，内丛状带上方的一些神经元向内丛状带的相反方向延伸并发育树突。这些结果表明，Reelin信号缺陷小鼠神经元的异常定位至少部分是由突变皮质内丛状区的异常形成引起的。(C)2002 Wiley-Liss，Inc.
The Reelin molecule plays a fundamental role in corticogenesis. After Reelin binds to its receptors, the Reelin signal is transduced through tyrosine phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). The reelin-gene-deficient mouse, reeler, and Dab1-deficient mouse, yotari, show disrupted positioning of neurons. Several molecules have been identified recently as being involved in Reelin signaling, however, the biological function of Reelin during cortical plate development was still unknown. We observed the migrating behavior of neurons during development in Reelin-signal-deficient mice. To visualize the migrating neurons directly, we introduced green fluorescent protein (GFP)-expression vectors into the ventricular zone with an in utero electroporation system and allowed the embryos to develop in utero until they were analyzed. The result showed that the migrating cells in the mutants were morphologically indistinguishable from those of normal mice. At the stage when the GFP-expressing cells reached the marginal zone near the pial surface and began dendrite formation in normal mice, the GFP-positive cells were found at various deeper positions in the mutant cortex. They had the morphology of migrating cells extending leading processes toward the pial surface. By contrast, in the mutants these cells tended to stop migration along the borders of the internal plexiform zone, the irregular structure consisting mainly of dendrites in the mutant cortex. Postnatally, these neurons began to develop dendrites later than the cells in the normal cortex. During this process, some neurons above the internal plexiform zone extended and developed dendrites in the opposite direction into the internal plexiform zone. These results suggest that the abnormal positioning of neurons in the Reelin-signal-deficient mice is caused, at least in part, by abnormal formation of the internal plexiform zone in the mutant cortex. (C) 2002 Wiley-Liss, Inc.