TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding
TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding
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DOI：
10.1038/nn.3525
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发表时间：
2013-11-01
影响因子：
25
通讯作者：
Miyata, Takaki
中科院分区：
文献类型：
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作者：
Okamoto, Mayumi;Namba, Takashi;Miyata, Takaki
神经祖细胞表现出细胞周期依赖的沿顶基底轴沿着的核间迁移（INM）。尽管最近在了解其潜在的分子机制方面取得了进展，但INM在机械上做出贡献的过程以及由祖细胞的顶基部伸长形态对INM的调节仍然不清楚。我们发现细胞表面分子TAG-1的敲低导致新皮层祖细胞基底突起的回缩。高度缩短的干细胞样祖细胞未能进行向基底INM，并在脑室周围（心尖下）空间变得过度拥挤。令人惊讶的是，过度拥挤的祖细胞离开顶端表面，迁移到基底神经元领土。这些观察结果，连同在toto成像和物理测试的结果，表明祖细胞可能会感觉到过度的机械应力，并作出反应。虽然，出乎意料的是，异位祖细胞保持干细胞样，并继续顺序产生神经元，直到胚胎晚期，组织发生被严重破坏。因此，INM对于防止核及其胞体过度拥挤，从而确保正常的脑组织发生是必不可少的。
Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.