Stanfield B B, Cowan W M
J Comp Neurol. 1979 Jun 1;185(3):423-59. doi: 10.1002/cne.901850303.
The histogenesis, the time of origin and the pattern of migration of the cells in the hippocampus and dentate gyrus, have been studied in normal and reeler mice. The earliest indication of a defect in the reeler hippocampus is seen on the fifteenth embryonic day (E15) which is at least 24 hours after the first indication of a defect in the neocortex. It is not until E18, that the dentate gyrus shows signs of its incipient abnormality. It appears then, that in both the hippocampus and the dentate gyrus the gene defect first manifests itself at the stage at which the definitive cellular layers are assembled. Experiments involving the injection of 3H-thymidine (3H-TdR) at different developmental stages have confirmed that the site and rate of cellular proliferation in the reeler hippocampus and dentate gyrus are normal, as is the initial pattern of cell migration. However, in the reeler dentate gyrus, most postnatal cell proliferation occurs ectopically and in the hippocampus the normal "inside-out" sequence of neurogenesis is reversed, the earliest pyramidal cells generated coming to lie superficially within the stratum pyramidale and the later formed cells being added at progressively deeper levels. There is no discernible gradient in the time of origin of the granule cells in the radial dimension of the reeler dentate gyrus, whereas there is an obvious "outside-in" gradient in the normal animal. The characteristic gradients in cell proliferation seen in the transverse and longitudinal dimensions of the normal dentate gyrus are, however, also evident in the reeler mouse. Taken together, these observations suggest that the reeler gene exerts its effect on neuronal position only in the radial dimension, and does so at a stage of development subsequent to the proliferation and initial migration of the relevant neurons. Timm's sulfide silver preparations indicate that the characteristic staining patterns seen in the dentate gyrus and hippocampus appear at the same time, and mature at the same rate in normal and reeler mice.
在正常小鼠和reeler小鼠中，对海马体和齿状回中细胞的组织发生、起源时间及迁移模式进行了研究。在reeler海马体中最早出现缺陷的迹象是在胚胎第15天（E15），这比新皮层首次出现缺陷迹象至少晚24小时。直到E18，齿状回才显示出初期异常的迹象。由此看来，在海马体和齿状回中，基因缺陷首先在确定的细胞层组装阶段显现出来。在不同发育阶段注射3H-胸腺嘧啶核苷（3H-TdR）的实验证实，reeler海马体和齿状回中细胞增殖位点和速率是正常的，细胞迁移的初始模式也是正常的。然而，在reeler齿状回中，大多数出生后细胞增殖发生在异位，在海马体中，正常的神经发生“由内向外”顺序被颠倒，最早产生的锥体细胞位于锥体层表面，而后来形成的细胞则在逐渐加深的层面添加。在reeler齿状回的径向维度上，颗粒细胞起源时间没有明显梯度，而在正常动物中则有明显的“由外向内”梯度现象。不过，在正常齿状回的横向和纵向维度上看到的细胞增殖特征梯度在reeler小鼠中也很明显。综合这些观察结果表明，reeler基因仅在径向维度上对神经元位置产生影响，并且是在相关神经元增殖和初始迁移后的发育阶段发挥作用。Timm硫化银染色制剂表明，在正常小鼠和reeler小鼠中，齿状回和海马体中看到的特征性染色模式同时出现，且成熟速率相同。
