Fanto Manolis, Clayton Lesley, Meredith Jamie, Hardiman Kirsten, Charroux Bernard, Kerridge Stephen, McNeill Helen
Cancer Research UK (ICRF), London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Development. 2003 Feb;130(4):763-74. doi: 10.1242/dev.00304.
Fat is an atypical cadherin that controls both cell growth and planar polarity. Atrophin is a nuclear co-repressor that is also essential for planar polarity; however, it is not known what genes Atrophin controls in planar polarity, or how Atrophin activity is regulated during the establishment of planar polarity. We show that Atrophin binds to the cytoplasmic domain of Fat and that Atrophin mutants show strong genetic interactions with fat. We find that both Atrophin and fat clones in the eye have non-autonomous disruptions in planar polarity that are restricted to the polar border of clones and that there is rescue of planar polarity defects on the equatorial border of these clones. Both fat and Atrophin are required to control four-jointed expression. In addition our mosaic analysis demonstrates an enhanced requirement for Atrophin in the R3 photoreceptor. These data lead us to a model in which fat and Atrophin act twice in the determination of planar polarity in the eye: first in setting up positional information through the production of a planar polarity diffusible signal, and later in R3 fate determination.
Fat是一种非典型钙黏着蛋白,它既能控制细胞生长,又能控制平面极性。萎缩蛋白是一种核共抑制因子,对平面极性也至关重要;然而,目前尚不清楚萎缩蛋白在平面极性中控制哪些基因,也不清楚在平面极性建立过程中萎缩蛋白的活性是如何被调节的。我们发现萎缩蛋白与Fat的细胞质结构域结合,并且萎缩蛋白突变体与fat表现出强烈的遗传相互作用。我们发现,眼睛中的萎缩蛋白和fat克隆在平面极性上都有非自主性破坏,这种破坏仅限于克隆的极性边界,并且在这些克隆的赤道边界上平面极性缺陷得到了挽救。fat和萎缩蛋白都是控制四联体表达所必需的。此外,我们的镶嵌分析表明,R3光感受器对萎缩蛋白的需求增加。这些数据使我们得出一个模型,其中fat和萎缩蛋白在眼睛平面极性的确定中起两次作用:首先通过产生平面极性可扩散信号来建立位置信息,然后在R3命运决定中起作用。