A novel disruption of cortical development in p35-/- mice distinct from reeler

A novel disruption of cortical development in p35-/- mice distinct from reeler
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DOI:
10.1002/(sici)1096-9861(19980615)395:4
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发表时间:
1998-06-15
影响因子:
2.5
通讯作者:
Tsai, LH
Tsai, LH
中科院分区:
医学3区
文献类型:
--
作者:
Kwon, YT;Tsai, LH

文献摘要

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p35/cdk 5神经元特异性激酶复合物已被证明在皮层神经元的层状结构中起重要作用。缺乏p35或cdk 5的小鼠表现出破坏的皮质分层模式。我们以前表明,而不是正常的“由内而外”的皮层神经元的分层模式,皮层神经元分层从“由外向内”的p35突变小鼠。为了深入了解这些缺陷背后的机制,我们研究了皮质发育过程中形成的标志性结构的组织和p35(-/-)皮质神经元的迁移行为,通过使用溴脱氧尿苷标记。在本研究中,我们表明,reelin定位在边缘区是正常的p35突变小鼠。此外,前板分裂成边缘区和subplate正确,未能发生在reeler小鼠的发育事件。最后,最早出生的皮质板神经元的迁移在p35突变小鼠中是正常的;随后产生的皮质神经元保持在这些神经元下面。这些数据表明,p35/cdk 5激酶所需的皮质板神经元迁移过去预先存在的神经元,并采取浅表的位置,构成内-外分层秩序的皮质层压。(C)1998 Wiley-Liss,Inc.
The p35/cdk5 neuronal-specific kinase complex has been shown to play an important role in the laminar configuration of cortical neurons. Mice lacking either p35 or cdk5 exhibit a disrupted cortical lamination pattern. We showed previously that instead of the normal "inside-out" layering pattern of cortical neurons, cortical neurons are layered from "outside-in" in p35 mutant mice. To gain insight into the mechanisms that underlie these defects, we examined the organization of landmark structures formed during cortical development and the migratory behavior of p35(-/-) cortical neurons by using bromodeoxyuridine labeling. In the present study, we show that reelin localization in the marginal zone is normal in p35 mutant mice. Furthermore, the preplate splits into the marginal zone and subplate properly, a developmental event that fails to occur in reeler mice. Finally, the migration of the earliest born cortical plate neurons is normal in p35 mutant mice; cortical neurons subsequently generated remain underneath these neurons. These data suggest that the p35/cdk5 kinase is required for cortical plate neurons to migrate past preexisting neurons and take up superficial positions to constitute the inside-outside layering order of cortical lamination. (C) 1998 Wiley-Liss, Inc.