Simon Françoise, Fichelson Pierre, Gho Michel, Audibert Agnès
Université Pierre et Marie Curie-Paris 6, UMR 7622, Paris, France.
PLoS Genet. 2009 Aug;5(8):e1000594. doi: 10.1371/journal.pgen.1000594. Epub 2009 Aug 7.
Understanding the mechanisms that coordinate cell proliferation, cell cycle arrest, and cell differentiation is essential to address the problem of how "normal" versus pathological developmental processes take place. In the bristle lineage of the adult fly, we have tested the capacity of post-mitotic cells to re-enter the cell cycle in response to the overexpression of cyclin E. We show that only terminal cells in which the identity is independent of Notch pathway undergo extra divisions after CycE overexpression. Our analysis shows that the responsiveness of cells to forced proliferation depends on both Prospero, a fate determinant, and on the level of Notch pathway activity. Our results demonstrate that the terminal quiescent state and differentiation are regulated by two parallel mechanisms acting simultaneously on fate acquisition and cell cycle progression.
了解协调细胞增殖、细胞周期停滞和细胞分化的机制对于解决“正常”与病理发育过程如何发生的问题至关重要。在成年果蝇的刚毛谱系中,我们测试了有丝分裂后细胞响应细胞周期蛋白E过表达而重新进入细胞周期的能力。我们发现,只有身份独立于Notch信号通路的终末细胞在细胞周期蛋白E过表达后会进行额外的分裂。我们的分析表明,细胞对强制增殖的反应性取决于命运决定因子Prospero以及Notch信号通路的活性水平。我们的结果表明,终末静止状态和分化是由两个平行机制同时作用于命运获得和细胞周期进程来调节的。