Interkinetic nuclear migration and the selection of neurogenic cell divisions during vertebrate retinogenesis
Interkinetic nuclear migration and the selection of neurogenic cell divisions during vertebrate retinogenesis
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DOI：
10.1523/jneurosci.2754-07.2007
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发表时间：
2007-09-19
影响因子：
5.3
通讯作者：
Link, Brian A.
中科院分区：
文献类型：
--
作者：
Baye, Lisa M.;Link, Brian A.
在视网膜发育过程中，神经上皮祖细胞要么以对称增殖模式分裂，其中两个子细胞都保持有丝分裂，要么以神经源性模式分裂，其中至少一个子细胞退出细胞周期并分化为神经元。虽然神经发生的细胞机制尚不清楚，但细胞行为的异质性被认为会影响细胞的命运。在这项研究中，我们分析了细胞核的相互动力学迁移，细胞核在细胞周期中的顶基运动，以及这种细胞行为与神经发生的关系。利用斑马鱼的延时成像，我们发现在视网膜神经上皮细胞中，相互作用的核迁移的各种参数显着不均匀。我们提供的直接证据表明，神经源性祖细胞在最终有丝分裂前的最后一个细胞周期有更大的基底核迁移。此外，我们发现非典型蛋白激酶C （aPKC）介导的细胞极性对于核位置和神经发生之间的关系至关重要。aPKC的缺失也导致增殖性细胞分裂增加和视网膜神经发生减少。我们的数据支持了一种新的神经发生模型，在这种模型中，核的相互动力学迁移在神经上皮细胞中对细胞核进行了不同的定位，从而影响了基于顶基极化信号的细胞周期退出祖细胞的选择。
During retinal development, neuroepithelial progenitor cells divide in either a symmetric proliferative mode, in which both daughter cells remain mitotic, or in a neurogenic mode, in which at least one daughter cell exits the cell cycle and differentiates as a neuron. Although the cellular mechanisms of neurogenesis remain unknown, heterogeneity in cell behaviors has been postulated to influence this cell fate. In this study, we analyze interkinetic nuclear migration, the apical-basal movement of nuclei in phase with the cell cycle, and the relationship of this cell behavior to neurogenesis. Using time-lapse imaging in zebrafish, we show that various parameters of interkinetic nuclear migration are significantly heterogeneous among retinal neuroepithelial cells. We provide direct evidence that neurogenic progenitors have greater basal nuclei migrations during the last cell cycle preceding a terminal mitosis. In addition, we show that atypical protein kinase C (aPKC)-mediated cell polarity is essential for the relationship between nuclear position and neurogenesis. Loss of aPKC also resulted in increased proliferative cell divisions and reduced retinal neurogenesis. Our data support a novel model for neurogenesis, in which interkinetic nuclear migration differentially positions nuclei in neuroepithelial cells and therefore influences selection of progenitors for cell cycle exit based on apical-basal polarized signals.