Escudero Luis M, Freeman Matthew
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
BMC Dev Biol. 2007 Mar 2;7:13. doi: 10.1186/1471-213X-7-13.
Most differentiating cells are arrested in G1-phase of the cell cycle and this proliferative quiescence appears important to allow differentiation programmes to be executed. An example occurs in the Drosophila eye imaginal disc, where all cells are synchronized and arrested in G1 phase prior to making a fate choice either to initiate the first round of photoreceptor differentiation or to re-enter one terminal mitosis.
We have analysed the mechanism of this temporally regulated G1-phase in order to develop an integrated model of this proliferative regulation. We find that an overlapping set of cell cycle inhibitors combine to form an efficient barrier to cell cycle progression. This barrier depends on both the primary secreted signals that drive retinal development, Dpp and Hh. Each of these has distinct, as well as partially overlapping functions, in ensuring that Cyclin E and dE2F1 are kept in check. Additionally, inhibition of Cyclin A by Roughex is essential, and this regulation is independent of Dpp and Hh.
One implication of these results is to further support the idea that Cyclin A has important functions in S-phase entry as well as in mitosis. The unexpectedly complex network of regulation may reflect the importance of cells being uniformly ready to respond to the inductive signals that coordinate retinal differentiation.
大多数正在分化的细胞停滞于细胞周期的G1期，这种增殖静止状态对于执行分化程序似乎很重要。果蝇眼成虫盘就是一个例子，在那里所有细胞在做出命运选择之前都会同步并停滞于G1期，这个命运选择要么是启动第一轮光感受器分化，要么是重新进入一次终末有丝分裂。
为了建立这种增殖调控的整合模型，我们分析了这种受时间调控的G1期的机制。我们发现一组重叠的细胞周期抑制剂共同形成了一道有效的细胞周期进展屏障。这道屏障依赖于驱动视网膜发育的主要分泌信号Dpp和Hh。在确保细胞周期蛋白E（Cyclin E）和dE2F1受到抑制方面，它们各自具有独特的功能，也有部分重叠的功能。此外，Roughex对细胞周期蛋白A（Cyclin A）的抑制至关重要，而且这种调控独立于Dpp和Hh。
这些结果的一个意义在于进一步支持了细胞周期蛋白A在进入S期以及有丝分裂过程中具有重要功能这一观点。这种意外复杂的调控网络可能反映了细胞统一准备好对协调视网膜分化的诱导信号做出反应的重要性。
