Sp2 regulates late neurogenic but not early expansive divisions of neural stem cells underlying population growth in the mouse cortex
Sp2 regulates late neurogenic but not early expansive divisions of neural stem cells underlying population growth in the mouse cortex
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DOI：
10.1242/dev.186056
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发表时间：
2020-02-01
期刊：
影响因子：
4.6
通讯作者：
Ghashghaei, H. Troy
中科院分区：
文献类型：
--
作者：
Johnson, Caroline A.;Ghashghaei, H. Troy
从皮质干细胞的自我扩增到神经元和胶质细胞的产生的细胞和分子机制尚未完全了解，尽管它们对神经发育很重要。在这里，我们已经调查了转录因子特异性蛋白2（Sp2）的作用，在扩张和神经性分区的发展中的大脑皮层结合条件性遗传缺失与镶嵌分析与双标记（MADM）系统在小鼠。我们发现，在经历神经原性分裂的祖细胞中Sp2的丢失导致早期有丝分裂阶段的延长而导致有丝分裂延长。这种破坏与皮质中上层神经元群体的耗竭相关。相反，早期皮质神经干细胞在Sp2缺乏的情况下正常增殖和扩增。这些结果表明Sp2在神经干细胞和祖细胞中的阶段特异性需求，并揭示了皮质发育的早期扩张和后期神经发生期之间的机械差异。
Cellular and molecular mechanisms underlying the switch from self-amplification of cortical stem cells to neuronal and glial generation are incompletely understood, despite their importance for neural development. Here, we have investigated the role of the transcription factor specificity protein 2 (Sp2) in expansive and neurogenic divisions of the developing cerebral cortex by combining conditional genetic deletion with the mosaic analysis with double markers (MADM) system in mice. We find that loss of Sp2 in progenitors undergoing neurogenic divisions results in prolonged mitosis due to extension of early mitotic stages. This disruption is correlated with depletion of the populations of upper layer neurons in the cortex. In contrast, early cortical neural stem cells proliferate and expand normally in the absence of Sp2. These results indicate a stage-specific requirement for Sp2 in neural stem and progenitor cells, and reveal mechanistic differences between the early expansive and later neurogenic periods of cortical development.This article has an associated 'The people behind the papers' interview.