Six3 controls the neural progenitor status in the murine CNS
Six3 controls the neural progenitor status in the murine CNS
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DOI：
10.1093/cercor/bhm092
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发表时间：
2008-03-01
期刊：
影响因子：
3.7
通讯作者：
Malatesta, Paolo
中科院分区：
文献类型：
--
作者：
Appolloni, Irene;Calzolari, Filippo;Malatesta, Paolo
Six3 是一种属于 Six/so 家族的包含同源结构域的转录调节因子，在发育中的小鼠端脑中显示出明确的时空表达模式，表明它可能控制神经祖细胞特定亚群的发育。我们发现，逆转录病毒介导的 Six3 错误表达通过缩短细胞周期和延长扩增周期，同时将其维持在不成熟的前体状态，从而导致分离的皮质祖细胞的克隆扩增。我们的结果表明，在哺乳动物大脑中观察到的 Six3 过度表达所产生的影响严格取决于其 DNA 结合结构域的完整性，这表明 Six3 的作用可能完全依赖于其转录活性。体内胚胎端脑单个祖细胞中 Six3 表达的上调使它们保持未分化状态。我们的观察表明，Six3 在控制哺乳动物神经发生过程中特定前体群体的增殖和分化之间的微妙平衡方面发挥着作用。
Six3, a homeodomain-containing transcriptional regulator belonging to the Six/so family, shows a defined spatiotemporal expression pattern in the developing murine telencephalon, suggesting that it may control the development of specific subsets of neural progenitors. We find that retrovirus-mediated misexpression of Six3 causes clonal expansion of isolated cortical progenitor cells by shortening their cell cycle and by prolonging their amplification period, while maintaining them in an immature precursor state. Our results show that the observed effects exerted by Six3 overexpression in mammalian brain depend strictly on the integrity of its DNA-binding domain, suggesting that Six3 action likely relies exclusively on its transcriptional activity. In vivo upregulation of Six3 expression in single progenitor cells of the embryonic telencephalon keeps them in an undifferentiated state. Our observations point to a role of Six3 in the control of the subtle equilibrium between proliferation and differentiation of defined precursor populations during mammalian neurogenesis.