Kadowaki Masakazu, Nakamura Shoko, Machon Ondrej, Krauss Stefan, Radice Glenn L, Takeichi Masatoshi
Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501, Japan, and Institute of Medical Microbiology and Centre for Molecular Biology and Neuroscience, The National Hospital, Oslo, Norway.
Dev Biol. 2007 Apr 1;304(1):22-33. doi: 10.1016/j.ydbio.2006.12.014. Epub 2006 Dec 9.
The cerebral cortex is a complex laminated structure generated by the sequential migration of developing neurons from the ventricular zone. One of the molecules that may play a role in cortical morphogenesis is N-cadherin since its blocking causes disruption of the ordered arrangement of cells in other neural tissues, such as the neural retina. Here, we show that when the N-cadherin gene had been conditionally deleted in the mouse cerebral cortex, the intra-cortical structures were nearly completely randomized; e.g., mitotic cells and postmitotic cells were scattered throughout the cortex without any order. These defects seemed to mainly originate from the disruption of the adherens junctions (AJs) localized in the apical end of neuroepithelial cells, where N-cadherin is normally most highly concentrated. In the absence of N-cadherin, neuroepithelial or radial glial cells could not expand their bodies or processes to span the distance between the ventricular and pial surfaces and therefore terminated them in the middle zone of the cortex. These results demonstrate that N-cadherin is essential for maintaining the normal architecture of neuroepithelial or radial glial cells and that their disruption randomizes the internal structures of the cortex.
大脑皮层是一个复杂的分层结构,由发育中的神经元从脑室区依次迁移而形成。可能在皮层形态发生中起作用的分子之一是N-钙黏蛋白,因为其阻断会导致其他神经组织(如神经视网膜)中细胞的有序排列受到破坏。在这里,我们表明,当N-钙黏蛋白基因在小鼠大脑皮层中被条件性删除时,皮层内结构几乎完全随机化;例如,有丝分裂细胞和有丝分裂后细胞无序地散布在整个皮层中。这些缺陷似乎主要源于位于神经上皮细胞顶端的黏附连接(AJs)的破坏,而N-钙黏蛋白通常在那里高度集中。在没有N-钙黏蛋白的情况下,神经上皮细胞或放射状胶质细胞无法扩展其身体或突起以跨越脑室表面和软脑膜表面之间的距离,因此在皮层的中间区域终止。这些结果表明,N-钙黏蛋白对于维持神经上皮细胞或放射状胶质细胞的正常结构至关重要,并且它们的破坏会使皮层的内部结构随机化。