The developing central nervous system (CNS) is particularly prone to malignant transformation, but the underlying mechanisms remain unresolved. However, periods of tumor susceptibility appear to correlate with windows of increased proliferation, which are often observed during embryonic and fetal stages and reflect stereotypical changes in the proliferative properties of neural progenitors. The temporal mechanisms underlying these proliferation patterns are still unclear in mammals. In Drosophila, two decades of work have revealed a network of sequentially expressed transcription factors and RNA-binding proteins that compose a neural progenitor-intrinsic temporal patterning system. Temporal patterning controls both the identity of the post-mitotic progeny of neural progenitors, according to the order in which they arose, and the proliferative properties of neural progenitors along development. In addition, in Drosophila, temporal patterning delineates early windows of cancer susceptibility and is aberrantly regulated in developmental tumors to govern cellular hierarchy as well as the metabolic and proliferative heterogeneity of tumor cells. Whereas recent studies have shown that similar genetic programs unfold during both fetal development and pediatric brain tumors, I discuss, in this Review, how the concept of temporal patterning that was pioneered in Drosophila could help to understand the mechanisms of initiation and progression of CNS tumors in children.

中文翻译：

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神经祖细胞的时间模式：从果蝇发育到儿童癌症。

发育中的中枢神经系统 (CNS) 特别容易发生恶性转化，但其潜在机制仍未得到解决。然而，肿瘤易感期似乎与增殖增加的窗口相关，这通常在胚胎和胎儿阶段观察到，反映了神经祖细胞增殖特性的刻板变化。在哺乳动物中，这些增殖模式背后的时间机制仍不清楚。在果蝇中，二十年的工作揭示了一个由顺序表达的转录因子和 RNA 结合蛋白组成的网络，它们构成了神经祖细胞内在的时间模式系统。时间模式控制神经祖细胞有丝分裂后后代的身份，根据它们出现的顺序，以及神经祖细胞在发育过程中的增殖特性。此外，在果蝇中，时间模式描绘了癌症易感性的早期窗口，并且在发育性肿瘤中受到异常调节，以控制细胞层次结构以及肿瘤细胞的代谢和增殖异质性。尽管最近的研究表明，类似的遗传程序在胎儿发育和小儿脑肿瘤期间展开，但我在本综述中讨论了在果蝇中开创的时间模式概念如何有助于理解中枢神经系统肿瘤的发生和发展机制在儿童中。