Borrell V, Del Río J A, Alcántara S, Derer M, Martínez A, D'Arcangelo G, Nakajima K, Mikoshiba K, Derer P, Curran T, Soriano E
Department of Animal and Plant Cell Biology, University of Barcelona, Barcelona 08028, Spain.
J Neurosci. 1999 Feb 15;19(4):1345-58. doi: 10.1523/JNEUROSCI.19-04-01345.1999.
Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.
在此，我们研究了Reelin（一种参与神经元迁移的细胞外蛋白）在海马体连接形成中的作用。在产前和产后阶段，在缺乏Reelin的reeler突变小鼠的海马体中，内嗅投射的一般分层和拓扑分布得以保留。然而，发育中的和成年的内嗅传入纤维显示出严重改变，包括错误导向纤维数量增加以及内侧和外侧内嗅皮质形成异常的终末斑。在围产期阶段，reeler小鼠中的单个内嗅轴突聚集成粗束，并且它们的轴突分支减少，轴突侧支的延伸也减少。我们还表明，在发育过程中，reeler小鼠的内嗅-海马突触数量比对照动物少。对来自reeler和野生型小鼠切片的混合内嗅-海马共培养物进行的研究表明，这些异常是由目标海马体中缺乏Reelin引起的。这些发现意味着Reelin在海马体中特定层和拓扑连接的形成过程中发挥调节作用。它们还表明，Reelin促进内嗅传入纤维的单纤维成熟和突触形成。
