Foran D R, Peterson A C
Department of Neurology and Neurosurgery, and Molecular Oncology, McGill University, Montreal, Quebec, Canada.
J Neurosci. 1992 Dec;12(12):4890-7. doi: 10.1523/JNEUROSCI.12-12-04890.1992.
Myelin has pronounced effects upon the morphology, function, and growth of axons in the mammalian CNS. Consequently, oligodendrocyte development and myelination have been investigated using a wide variety of histological, immunocytochemical, ultrastructural, and biochemical techniques. While many of the spatial and temporal features of myelin appearance have been characterized, for any one species only limited regions of the CNS have been investigated. To address this limitation, we have derived transgenic mice in which the bacterial Lac Z gene is regulated by promoter elements of the myelin basic protein gene. When differentiating oligodendrocytes begin to elaborate recognizable myelin, they initiate expression of the MBP-Lac Z transgene and accumulate readily detectable levels of beta-galactosidase. Here, we exploit the sensitivity, resolution, and ease of beta-galactosidase histochemical assays to characterize the temporal and spatial patterns of CNS myelination in the mouse. Many features of the myelination program revealed by this approach were predicted by the immunocytochemical and ultrastructural data derived from other species. Nonetheless, previously undocumented patterns were also encountered. beta-Galactosidase was expressed first by oligodendrocytes in the ventral spinal cord, 1 d prior to birth. There, myelination proceeded in a strictly rostral-caudal direction, whereas in the dorsal cord, myelination initiated in the cervical enlargement and proceeded in both rostral and caudal directions. In the cerebellum, deep regions myelinated first, and in the optic nerve, myelination initiated at the retinal end. In contrast, the lateral olfactory tracts, pons, and optic chiasm initiated myelination along their entire course.(ABSTRACT TRUNCATED AT 250 WORDS)
髓磷脂对哺乳动物中枢神经系统中轴突的形态、功能及生长具有显著影响。因此,人们运用了多种组织学、免疫细胞化学、超微结构及生化技术来研究少突胶质细胞的发育和髓鞘形成。尽管髓磷脂出现的许多时空特征已得到描述,但对于任何一个物种而言,仅对中枢神经系统的有限区域进行了研究。为解决这一局限性,我们培育出了转基因小鼠,其中细菌Lac Z基因受髓磷脂碱性蛋白基因的启动子元件调控。当分化的少突胶质细胞开始形成可识别的髓磷脂时,它们启动MBP-Lac Z转基因的表达,并积累易于检测到的β-半乳糖苷酶水平。在此,我们利用β-半乳糖苷酶组织化学检测的敏感性、分辨率和简便性来描述小鼠中枢神经系统髓鞘形成的时空模式。通过这种方法揭示的髓鞘形成程序的许多特征可由源自其他物种免疫细胞化学和超微结构数据预测。尽管如此,也遇到了以前未记录的模式。β-半乳糖苷酶首先由出生前1天的脊髓腹侧少突胶质细胞表达。在那里,髓鞘形成严格按照头-尾方向进行,而在脊髓背侧,髓鞘形成始于颈膨大,并向头侧和尾侧两个方向进行。在小脑中,深部区域首先形成髓鞘,而在视神经中,髓鞘形成始于视网膜端。相比之下,外侧嗅束、脑桥和视交叉在其整个行程中开始形成髓鞘。(摘要截短于250词)