Sun Jianjun, Deng Wu-Min
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Dev Cell. 2007 Mar;12(3):431-42. doi: 10.1016/j.devcel.2007.02.003.
Temporal and spatial regulation of proliferation and differentiation by signaling pathways is essential for animal development. Drosophila follicular epithelial cells provide an excellent model system for the study of temporal regulation of cell proliferation. In follicle cells, the Notch pathway stops proliferation and promotes a switch from the mitotic cycle to the endocycle. Here, we show that zinc-finger transcription factor Hindsight mediates the role of Notch in regulating cell differentiation and the switch of cell-cycle programs. Hindsight is required and sufficient to stop proliferation and induce the transition to the endocycle. To do so, it represses string, Cut, and Hedgehog signaling, which promote proliferation during early oogenesis. Hindsight, along with another zinc-finger protein, Tramtrack, downregulates Hedgehog signaling through transcriptional repression of cubitus interruptus. Our studies suggest that Hindsight bridges the two antagonistic pathways, Notch and Hedgehog, in the temporal regulation of follicle-cell proliferation and differentiation.
信号通路对增殖和分化的时空调控对于动物发育至关重要。果蝇卵泡上皮细胞为研究细胞增殖的时间调控提供了一个出色的模型系统。在卵泡细胞中，Notch信号通路会停止增殖并促进从有丝分裂周期向末期循环的转变。在此，我们表明锌指转录因子indsight介导了Notch在调节细胞分化和细胞周期程序转换中的作用。indsight是停止增殖并诱导向末期循环转变所必需且充分的。为此，它会抑制string、Cut和Hedgehog信号，这些信号在早期卵子发生过程中促进增殖。indsight与另一种锌指蛋白Tramtrack一起，通过对间断翅脉的转录抑制来下调Hedgehog信号。我们的研究表明，indsight在卵泡细胞增殖和分化的时间调控中连接了Notch和Hedgehog这两条拮抗通路。
