Variant cell cycles regulated by Notch signaling control cell size and ensure a functional blood-brain barrier.
Variant cell cycles regulated by Notch signaling control cell size and ensure a functional blood-brain barrier.
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DOI：
10.1242/dev.157115
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发表时间：
2018-02-13
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影响因子：
--
通讯作者：
Orr-Weaver TL
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作者：
Von Stetina JR;Frawley LE;Unhavaithaya Y;Orr-Weaver TL
细胞大小的调节对发育至关重要。在植物和动物中，两种细胞周期变异通过增加倍性来产生大细胞：内周期和内丝分裂。选择哪一个周期背后的原理是未知的。我们表明，在果蝇神经系统中，神经周下胶质细胞（SPG）在使用内循环和内膜分裂生长方面是独一无二的。在大脑中，大多数SPG最初是内循环的，然后在幼虫发育过程中转变为内膜分裂。Notch信号通路和Cdc25磷酸酶在胞内周期和内膜分裂的选择中起着至关重要的作用，为细胞从一种转变为另一种提供了实验手段。这揭示了对细胞大小和内膜分裂细胞特性的控制的基本见解。有质分裂细胞比内环细胞具有更高的倍性和更大的体积，并且有质分裂的SPG是血脑屏障所必需的。Notch信号的减少甚至在通常为单核的腹侧神经索SPG中也能促进内膜分裂，但在内环的唾液腺细胞中却没有，揭示了组织特异性的细胞周期反应。在果蝇脑叶中，Notch和有丝分裂激活磷酸酶串在幼虫发育过程中调节神经周下胶质细胞从胞内周期向胞内分裂的转换，使胞内分裂细胞获得增加的倍性和大小。
Regulation of cell size is crucial in development. In plants and animals two cell cycle variants are employed to generate large cells by increased ploidy: the endocycle and endomitosis. The rationale behind the choice of which of these cycles is implemented is unknown. We show that in the Drosophila nervous system the subperineurial glia (SPG) are unique in using both the endocycle and endomitosis to grow. In the brain, the majority of SPG initially endocycle, then switch to endomitosis during larval development. The Notch signaling pathway and the String Cdc25 phosphatase are crucial for the endocycle versus endomitosis choice, providing the means experimentally to change cells from one to the other. This revealed fundamental insights into the control of cell size and the properties of endomitotic cells. Endomitotic cells attain a higher ploidy and larger size than endocycling cells, and endomitotic SPG are necessary for the blood-brain barrier. Decreased Notch signaling promotes endomitosis even in the ventral nerve cord SPG that normally are mononucleate, but not in the endocycling salivary gland cells, revealing tissue-specific cell cycle responses. In Drosophila brain lobes, Notch and the mitosis-activating phosphatase String regulate the switch of subperineurial glia from endocycle to endomitosis during larval development, with endomitotic cells attaining increased ploidy and size.