title: The sterile 20-like kinase tao controls tissue homeostasis by regulating the hippo pathway in Drosophila adult midgut.
abstract: 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, Diap1 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.
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Fangfei
authors.initials: F
authors.lastname: He
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Renling
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Miao
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Longjin
authors.initials: L
authors.lastname: Jin
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Capital Normal University, Beijing 100048, China. Electronic address: zhli@cnu.edu.cn.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China; State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati 45229, USA. Electronic address: xinhua.lin@cchmc.org.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000172:deficiency / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053612:Janus Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D050791:STAT Transcription Factors; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C556036:Tao protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Drosophila; Hippo; Midgut; Stem cell; Tao; Tissue homeostasis