The Hippo signaling pathway is widely considered a master regulator of organ growth because of the prominent overgrowth phenotypes caused by experimental manipulation of its activity. Contrary to this model, we show here that removing Hippo transcriptional output did not impair the ability of the mouse liver and Drosophila eyes to grow to their normal size. Moreover, the transcriptional activity of the Hippo pathway effectors Yap/Taz/Yki did not correlate with cell proliferation, and hyperactivation of these effectors induced gene expression programs that did not recapitulate normal development. Concordantly, a functional screen in Drosophila identified several Hippo pathway target genes that were required for ectopic overgrowth but not normal growth. Thus, Hippo signaling does not instruct normal growth, and the Hippo-induced overgrowth phenotypes are caused by the activation of abnormal genetic programs.

中文翻译：

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河马信号指示异位而非正常器官生长

Hippo 信号通路被广泛认为是器官生长的主要调节因子，因为对其活性的实验操作会导致显着的过度生长表型。与该模型相反，我们在此表明​​，去除 Hippo 转录输出不会损害小鼠肝脏和果蝇眼睛长到正常大小。此外，Hippo 通路效应子 Yap/Taz/Yki 的转录活性与细胞增殖无关，这些效应子的过度激活诱导的基因表达程序不会概括正常发育。一致地，一个功能屏幕果蝇确定了几个 Hippo 通路靶基因，这些基因是异位过度生长而不是正常生长所必需的。因此，Hippo 信号不指示正常生长，Hippo 诱导的过度生长表型是由异常遗传程序的激活引起的。