Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse
Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse
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Reeler 突变小鼠发育小脑中浦肯野细胞迁移受阻
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
K. Kawamura
中科院分区：
文献类型：
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作者：
S. Yuasa;J. Kitoh;S. Oda;K. Kawamura
人们认为，卷轴突变小鼠大脑中的皮质畸形是由于发育过程中神经母细胞迁移过程中的缺陷造成的。我们利用蒲肯野细胞的特异性标记物和放射状胶质细胞的标记物，用免疫组织化学和电子显微镜观察了蒲肯野细胞在卷轴突变体的小脑原基中的迁移过程。为了便于在胚胎阶段识别卷轴突变(R1)的纯合子，我们通过杂交和回交将携带常染色体半显性突变锤趾(HM)的染色体引入到卷轴突变的杂合子中，该杂合子是一种常染色体隐性遗传，位于同源染色体上。利用该双杂合品系(+/rl-Hm/+)，可以通过正常的足部外观从产仔中筛选出rl纯合子。杂合子rl胚胎和非携带者都含有HM基因，并表现为HM表型，足畸形可从妊娠第15天开始识别。在对照小鼠的小脑原基中，浦肯野细胞从脑室带向皮质径向迁移。相反，大多数迁移性浦肯野细胞仍留在中间带，它们向皮质的迁移在卷轴突变体的小脑中受阻。用抗神经元-神经胶质黏附分子Tenascin抗体和标记未成熟星形胶质细胞标志的单抗1D11标记，在小脑原基显示放射状胶质细胞突起和胞体排列紊乱。电子显微镜观察显示，在对照小脑的中间区，迁移细胞与放射状定向的神经胶质突起相贴合。相反，游走性神经母细胞的主导突起与放射状胶质细胞杂乱无章的突起在卷曲小脑的中间带中被观察到。这些结果提示，小脑皮质蒲肯野细胞迁移受阻和排列紊乱是由于放射状胶质细胞发育不全和发育异常，导致蒲肯野细胞迁移过程中接触导向障碍所致。
It has been considered that cortical malformation in the brain of the reeler mutant mouse is due to a defect in the process of neuroblast migration during development. We examined the process of Purkinje cell migration in the cerebellar primordium of the reeler mutant immunohistochemically and electron-microscopically, employing a specific marker for Purkinje cells and markers for radial glia. To facilitate the recognition of the homozygote of the reeler mutation (r1) at the embryonic stage, we introduced the chromosome carrying the autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross into the heterozygote of the reeler mutation, which is an autosomal recessive and located on the homologous chromosome. Using this double heterozygous strain (+/rl-Hm/+), the homozygote of rl can be selected from littermates by the normal appearance of the feet. Both the heterozygous rl embryos and non-carriers harbor the Hm locus and show the Hm phenotype as a deformity of the feet that can be recognized from the 15th day of gestation. In the cerebellar primordium of control mice, Purkinje cells migrated radially from the ventricular zone towards the cortex. In contrast, most of the migratory Purkinje cells remained in the intermediate zone, and their migration towards the cortex was obstructed in the cerebellum of the reeler mutant. A disorganized arrangement of both the processes and cell bodies of the radial glia was demonstrated in the cerebellar primordium of the reeler by labeling them with the antibody against tenascin, a neuron-glial adhesion molecule, and the monoclonal antibody 1D11, a marker for immature astroglia. Electron-microscopic observations revealed apposition of the migratory cells to the radially oriented glial processes in the intermediate zone of the control cerebellum. In contrast, the apposition of leading processes of the migratory neuroblasts to disorganized processes of the radial glia was observed in the intermediate zone of the reeler cerebellum. These findings suggest that the obstructed migration and disordered cortical alignment of Purkinje cells in the reeller cerebellum is due to dysgenesis and abnormal development of radial glia, resulting in disturbance of contact guidance in the process of Purkinje cell migration.