Borrell V, Ruiz M, Del Río J A, Soriano E
Department of Animal and Plant Cell Biology, University of Barcelona, Diagonal 645, Barcelona, 08028, Spain.
Exp Neurol. 1999 Apr;156(2):268-82. doi: 10.1006/exnr.1999.7022.
Reelin is a large, extracellular matrix protein involved in neuronal migration and axonal growth. To analyze the contribution of Reelin to the development of the commissural projection in the hippocampus, we analyzed the ontogeny of this projection in the reeler mutant mouse. Injections of the lipophilic tracer DiI revealed many commissural fibers in the hippocampus of both reeler and control mice at P1-P2. At P5, at P12, and in the adult, the topography of commissural connections was normal in the CA1 region of reeler mice, with axons innervating the stratum radiatum and stratum oriens. In contrast, in the CA3/CA2 region, commissural fibers abnormally innervated the stratum lacunosum-moleculare and, in the dentate gyrus, some fibers were observed in the outer molecular layer. Next, we monitored the distribution of Cajal-Retzius cells in the hippocampus of reeler mutant mice and noted that the stratum lacunosum-moleculare of the CA3/CA2 region was largely devoid of Cajal-Retzius (CR) cells. Taken together, the above results indicate that in the absence of CR cells in the CA3/CA2, commissural axons abnormally grow to the stratum lacunosum-moleculare. To test this hypothesis a series of coculture experiments was performed in collagen gels, in which the CA3 axonal growth was monitored when confronted to the marginal zone. These experiments showed that the marginal zone containing CR cells exerts short-range inhibitory influences for commissural axonal growth.
Reelin是一种大型细胞外基质蛋白，参与神经元迁移和轴突生长。为了分析Reelin对海马连合投射发育的贡献，我们在reeler突变小鼠中分析了该投射的个体发生。注射亲脂性示踪剂DiI显示，在出生后第1至2天，reeler小鼠和对照小鼠的海马中都有许多连合纤维。在出生后第5天、第12天以及成年期，reeler小鼠CA1区域的连合连接拓扑结构正常，轴突支配辐射层和原层。相比之下，在CA3/CA2区域，连合纤维异常支配腔隙分子层，并且在齿状回中，在外分子层观察到一些纤维。接下来，我们监测了reeler突变小鼠海马中Cajal-Retzius细胞的分布，并注意到CA3/CA2区域的腔隙分子层基本上没有Cajal-Retzius（CR）细胞。综上所述，上述结果表明，在CA3/CA2区域缺乏CR细胞的情况下，连合轴突异常生长至腔隙分子层。为了验证这一假设，我们在胶原凝胶中进行了一系列共培养实验，在实验中当CA3轴突与边缘区接触时监测其生长情况。这些实验表明，含有CR细胞的边缘区对连合轴突生长施加短程抑制作用。
