Spitzer Danielle C, Sun William Y, Rodríguez-Vargas Anthony, Hariharan Iswar K
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Development. 2025 Aug 1;152(15). doi: 10.1242/dev.204572. Epub 2025 Aug 7.
The growth and survival of cells depends both on their intrinsic properties and interactions with their neighbors. In a screen of genes encoding cell-surface proteins for knockdowns that affect clone size or shape in mosaic Drosophila imaginal discs, we found that clones with reduced echinoid (ed) function are fewer and smaller, and are frequently eliminated during development. This elimination results, in significant part, from increased levels of apoptosis due to decreased Diap1 protein. We found that Hippo pathway activity is not decreased in ed mutant cells, as previously claimed, but is decreased in some of their immediate wild-type neighbors, consistent with the observed elimination of ed clones by a mechanism resembling cell competition. In contrast to the underrepresentation of ed clones, discs or compartments composed of mostly ed mutant tissue overgrow, despite having increased levels of apoptosis. The overgrowth results from a failure to arrest growth at the appropriate final size during an extended larval stage. Thus, ed has two distinct functions: an anti-apoptotic function via maintenance of Diap1 levels, and a function to arrest growth at the appropriate final size.
细胞的生长和存活既取决于其内在特性，也取决于与相邻细胞的相互作用。在一项针对编码细胞表面蛋白的基因进行的筛选中，我们通过敲低这些基因来影响镶嵌果蝇成虫盘的克隆大小或形状，发现棘皮动物（echinoid，ed）功能降低的克隆数量减少且体积变小，并且在发育过程中经常被消除。这种消除在很大程度上是由于Diap1蛋白水平降低导致凋亡水平升高所致。我们发现，Hippo信号通路活性在ed突变细胞中并未如先前声称的那样降低，而是在其一些紧邻的野生型邻居中降低，这与通过类似于细胞竞争机制观察到的ed克隆消除现象一致。与ed克隆数量不足相反，尽管凋亡水平升高，但主要由ed突变组织组成的盘或隔室会过度生长。这种过度生长是由于在延长的幼虫阶段未能在适当的最终大小停止生长所致。因此，ed具有两种不同的功能：通过维持Diap1水平发挥抗凋亡功能，以及在适当的最终大小停止生长的功能。
