The Sterile 20-Like Kinase Tao Controls Tissue Homeostasis by Regulating the Hippo Pathway in Drosophila Adult Midgut

• Published in: Journal of genetics and genomics 2014-08, Vol.41 (8), p.429-438
• Main Authors: Huang, Xudong, Shi, Lai, Cao, Jun, He, Fangfei, Li, Renling, Zhang, Yan, Miao, Shuang, Jin, Longjin, Qu, Jia, Li, Zhouhua, Lin, Xinhua
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - metabolism; Drosophila Proteins - deficiency; Drosophila Proteins - metabolism; Female; Hippo; Homeostasis; Intestinal Mucosa - metabolism; Intestines - cytology; Intracellular Signaling Peptides and Proteins - metabolism; Janus Kinases - metabolism; Janus激酶; Midgut; Nuclear Proteins - metabolism; Protein-Serine-Threonine Kinases - deficiency; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction; STAT Transcription Factors - metabolism; Stem cell; Stem Cells - cytology; Tao; Tissue homeostasis; Trans-Activators - metabolism; 平衡; 果蝇; 河马; 稳态控制; 组织; 肠道; 通路
• ISSN: 1673-8527
• DOI: 10.1016/j.jgg.2014.05.007

The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.