Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21064-9. doi: 10.1073/pnas.1012759107. Epub 2010 Nov 15.
Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis and replenishing lost cells in response to tissue damage. Here we demonstrate that the Hippo (Hpo) signaling pathway, an evolutionarily conserved pathway implicated in organ size control and tumorigenesis, plays an essential role in regulating ISC proliferation. Loss of Hpo signaling in either midgut precursor cells or epithelial cells stimulates ISC proliferation. We provide evidence that loss of Hpo signaling in epithelial cells increases the production of cytokines of the Upd family and multiple EGFR ligands that activate JAK-STAT and EGFR signaling pathways in ISCs to stimulate their proliferation, thus revealing a unique non-cell-autonomous role of Hpo signaling in blocking ISC proliferation. Finally, we show that the Hpo pathway mediator Yorkie (Yki) is also required in precursor cells for injury-induced ISC proliferation in response to tissue-damaging reagent DSS.
果蝇成体肠道中的肠干细胞（ISCs）对于维持组织内稳态和响应组织损伤补充丢失的细胞是必需的。在这里，我们证明 Hippo（Hpo）信号通路，一种在器官大小控制和肿瘤发生中起作用的进化上保守的途径，在调节 ISC 增殖中起着至关重要的作用。Hpo 信号通路在肠道前体细胞或上皮细胞中的缺失会刺激 ISC 增殖。我们提供的证据表明，上皮细胞中 Hpo 信号通路的缺失会增加 Upd 家族细胞因子和多个 EGFR 配体的产生，这些配体激活 ISC 中的 JAK-STAT 和 EGFR 信号通路，从而刺激其增殖，从而揭示了 Hpo 信号通路在阻止 ISC 增殖中的独特非细胞自主作用。最后，我们发现 Hpo 途径介体 Yorkie（Yki）在前体细胞中对于损伤诱导的 ISC 增殖也是必需的，以响应组织损伤试剂 DSS。
