Howard Florey Institute, University of Melbourne, Parkville 3010, Victoria, Australia.
Cereb Cortex. 2010 Sep;20(9):2017-26. doi: 10.1093/cercor/bhp287. Epub 2010 Jan 6.
Reelin is an important protein that is indispensable for cortical lamination. In the absence of Reelin, cortical layers fail to form due to inappropriate neuron migration and positioning. The inversion of cortical layers is attributed to failure of neurons to migrate past earlier-generated neurons although how Reelin-insufficiency causes this is unclear. The issue is complicated by recent studies showing that very little Reelin is required for cortical layering. To test how variation in the number of Reelin-producing cells is linked to cortical lamination, we have employed Reelin(+/+) <--> Reelin(-/-) chimeras in which the number of Reelin-expressing neurons is adjusted. We found that the Reeler phenotype was rescued in chimeras with a large contribution of Reelin(+/+) neurons; conversely in chimeras with a weak contribution by Reelin(+/+) neurons, the mutant phenotype remained. However, increasing the number of Reelin(+/+) neurons beyond an unknown threshold resulted in partial rescue, with the formation of a correctly layered secondary cortex lying on top of an inverted mutant cortex. Therefore, the development of cortical layers in the correct order requires a minimal level of Reelin protein to be present although paradoxically, this is insufficient to prevent the simultaneous formation of inverted cortical layers in the same hemisphere.
Reelin 是一种重要的蛋白质,对于皮质分层是不可或缺的。在 Reelin 缺失的情况下,由于神经元迁移和定位不当,皮质层无法形成。皮质层的反转归因于神经元无法越过早期产生的神经元迁移,尽管不清楚 Reelin 缺乏如何导致这种情况。最近的研究表明,皮质分层只需要很少的 Reelin,这使得问题变得更加复杂。为了测试 Reelin 产生细胞数量的变化与皮质分层的关系,我们利用 Reelin(+/+) <--> Reelin(-/-) 嵌合体来调整 Reelin 表达神经元的数量。我们发现,在 Reelin(+/+)神经元大量存在的嵌合体中,Reeler 表型得到了挽救;相反,在 Reelin(+/+)神经元贡献较弱的嵌合体中,突变表型仍然存在。然而,增加 Reelin(+/+)神经元的数量超过一个未知的阈值会导致部分挽救,形成一个正确分层的次级皮质层,位于反转的突变皮质层之上。因此,皮质层按正确顺序发育需要存在最低水平的 Reelin 蛋白,但矛盾的是,这不足以防止同一半球同时形成反转的皮质层。