Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning.
Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning.
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DOI：
10.1242/dev.134213
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发表时间：
2016-07-01
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影响因子：
--
通讯作者：
Baum B
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文献类型：
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作者：
Hunter GL;Hadjivasiliou Z;Bonin H;He L;Perrimon N;Charras G;Baum B
协调细胞分化与细胞生长和分裂对于多细胞组织的成功发育、稳态和再生至关重要。在这里，我们使用果蝇中的鬃毛图案作为模型系统来探索细胞周期进程和细胞命运决策的调节和功能耦合。刚毛和介入上皮细胞 (EC) 的模式是通过细胞周期 G2 期期间 Notch 介导的侧向抑制而建立的，因为相邻细胞通过侧向接触和/或基底突起彼此物理相互作用。由于Notch信号控制Cdc25下游的细胞分裂时间，与表达Delta的细胞横向接触的EC会经历更高水平的Notch信号并首先分裂，然后是更远的邻居，最后是表达Delta的细胞。相反，有丝分裂进入和细胞分裂使内皮细胞对侧抑制信号产生抵抗，从而决定了它们的命运。通过实验和计算模型的结合，我们证明了Notch信号传导和细胞周期进程之间的这种相互关系就像一个发育时钟，提供了一个限定的时间窗口，在此期间细胞决定它们的命运，确保有效和有序的鬃毛图案。摘要：在果蝇 notum 中，Notch 信号传导和细胞周期进程之间的相互关系就像时钟一样，提供了细胞决定其命运的有限时间窗口。
Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning. Summary: In the fly notum, a reciprocal relationship between Notch signalling and cell cycle progression acts like a clock, providing a delimited window of time during which cells decide their fate.