Li Xue, Perissi Valentina, Liu Forrest, Rose David W, Rosenfeld Michael G
Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA.
Science. 2002 Aug 16;297(5584):1180-3. doi: 10.1126/science.1073263. Epub 2002 Jul 18.
Mammalian organogenesis requires the expansion of pluripotent precursor cells before the subsequent determination of specific cell types, but the tissue-specific molecular mechanisms that regulate the initial expansion of primordial cells remain poorly defined. We have genetically established that Six6 homeodomain factor, acting as a strong tissue-specific repressor, regulates early progenitor cell proliferation during mammalian retinogenesis and pituitary development. Six6, in association with Dach corepressors, regulates proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. These data reveal a molecular mechanism by which a tissue-specific transcriptional repressor-corepressor complex can provide an organ-specific strategy for physiological expansion of precursor populations.
哺乳动物器官发生需要多能前体细胞在随后特定细胞类型确定之前进行扩增，但调节原始细胞初始扩增的组织特异性分子机制仍不清楚。我们通过遗传学方法确定，Six6同源结构域因子作为一种强大的组织特异性抑制因子，在哺乳动物视网膜发生和垂体发育过程中调节早期祖细胞增殖。Six6与Dach共抑制因子结合，通过直接抑制细胞周期蛋白依赖性激酶抑制剂（包括p27Kip1启动子）来调节增殖。这些数据揭示了一种分子机制，即组织特异性转录抑制因子-共抑制因子复合物可以为前体细胞群体的生理扩增提供一种器官特异性策略。
