Kwon Y T, Tsai L H
Howard Hughes Medical Institute and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Comp Neurol. 1998 Jun 15;395(4):510-22. doi: 10.1002/(sici)1096-9861(19980615)395:4<510::aid-cne7>3.0.co;2-4.
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.
p35/cdk5神经元特异性激酶复合物已被证明在皮质神经元的分层结构中起重要作用。缺乏p35或cdk5的小鼠表现出皮质分层模式紊乱。我们之前表明，在p35突变小鼠中，皮质神经元不是正常的“由内向外”分层模式，而是“由外向内”分层。为了深入了解这些缺陷背后的机制，我们通过使用溴脱氧尿苷标记来检查皮质发育过程中形成的标志性结构的组织以及p35(-/-)皮质神经元的迁移行为。在本研究中，我们表明在p35突变小鼠中，边缘区的Reelin定位是正常的。此外，前板正常分裂为边缘区和亚板，而在reeler小鼠中这一发育事件无法发生。最后，最早生成的皮质板神经元在p35突变小鼠中的迁移是正常的；随后生成的皮质神经元则留在这些神经元下方。这些数据表明，p35/cdk5激酶是皮质板神经元迁移越过先前存在的神经元并占据表面位置以构成皮质分层的由内向外分层顺序所必需的。
