研究人员表示，Hippo信号通路被广泛认为是器官生长的核心调控因子，因为对其活性的实验操作造成了突出的过度生长表型。
与这种模式相反，研究人员表明，去除Hippo的转录输出并不损害小鼠肝脏和果蝇眼睛生长到正常大小的能力。此外，Hippo途径效应分子Yap/Taz/Yki的转录活性与细胞增殖不相关，这些效应分子的过度激活诱导的基因表达程序不能再现正常发育。一致的是，果蝇的功能筛选发现了几个Hippo通路的靶基因，这些基因是异位过度生长所需要的，而非正常生长。因此，Hippo信号不指导正常的生长，而Hippo诱导的过度生长表型是由异常遗传程序的激活引起的。
附：英文原文
Title: Hippo signaling instructs ectopic but not normal organ growth
Author: W. Kowalczyk, L. Romanelli, M. Atkins, H. Hillen, C. Bravo González-Blas, J. Jacobs, J. Xie, S. Soheily, E. Verboven, I. M. Moya, S. Verhulst, M. de Waegeneer, L. Sansores-Garcia, L. van Huffel, R. L. Johnson, L. A. van Grunsven, S. Aerts, G. Halder
Issue&Volume: 2022-11-18
Abstract: 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.
DOI: abg3679
Source: https://www.science.org/doi/10.1126/science.abg3679