Friedrichs Melanie, Larralde Osmany, Skutella Thomas, Theil Thomas
Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Dev Biol. 2008 Jun 1;318(1):203-14. doi: 10.1016/j.ydbio.2008.03.032. Epub 2008 Mar 28.
The layered organization of the cerebral cortex develops in an inside-out pattern, a process which is controlled by the secreted protein reelin. Here we report on cortical lamination in the Gli3 hypomorphic mouse mutant Xt(J)/Pdn which lacks the cortical hem, a major source of reelin(+) Cajal Retzius cells in the cerebral cortex. Unlike other previously described mouse mutants with hem defects, cortical lamination is disturbed in Xt(J)/Pdn animals. Surprisingly, these layering defects occur in the presence of reelin(+) cells which are probably derived from an expanded Dbx1(+) progenitor pool in the mutant. However, while these reelin(+) neurons and also Calretinin(+) cells are initially evenly distributed over the cortical surface they form clusters later during development suggesting a novel role for Gli3 in maintaining the proper arrangement of these cells in the marginal zone. Moreover, the radial glial network is disturbed in the regions of these clusters. In addition, the differentiation of subplate cells is affected which serve as a framework for developing a properly laminated cortex.
大脑皮层的分层组织以由内向外的模式发育，这一过程由分泌蛋白reelin控制。在此我们报道Gli3低表达小鼠突变体Xt(J)/Pdn的皮层分层情况，该突变体缺乏皮层下托，而皮层下托是大脑皮层中reelin(+) Cajal Retzius细胞的主要来源。与之前描述的其他具有皮层下托缺陷的小鼠突变体不同，Xt(J)/Pdn动物的皮层分层受到干扰。令人惊讶的是，这些分层缺陷出现在存在reelin(+)细胞的情况下，这些细胞可能源自突变体中扩大的Dbx1(+)祖细胞池。然而，虽然这些reelin(+)神经元以及钙视网膜蛋白(+)细胞最初均匀分布在皮层表面，但在发育后期它们会形成簇，这表明Gli3在维持这些细胞在边缘区的正确排列中具有新作用。此外，这些簇区域的放射状胶质细胞网络受到干扰。此外，作为发育出正常分层皮层框架的亚板层细胞的分化也受到影响。
