title: Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation.
abstract: Many stem cell populations are tightly regulated by their local microenvironment (niche), which comprises distinct types of stromal cells. However, little is known about mechanisms by which niche subgroups coordinately determine the stem cell fate. Here we identify that Yki, the key Hippo pathway component, is essential for escort cell (EC) function in promoting germline differentiation in Drosophila ovary. We found that Hedgehog (Hh) signals emanating primarily from cap cells support the function of ECs, where Cubitus interruptus (Ci), the Hh signaling effector, acts to inhibit Hippo kinase cascade activity. Mechanistically, we found that Ci competitively interacts with Hpo and impairs the Hpo-Wts signaling complex formation, thereby promoting Yki nuclear localization. The actions of Ci ensure effective Yki signaling to antagonize Sd/Tgi/Vg-mediated default repression in ECs. This study uncovers a mechanism explaining how subgroups of niche cells coordinate to determine the stem cell fate via Hh-Hippo signaling crosstalk, and enhances our understanding of mechanistic regulations of the oncogenic Yki/YAP signaling.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Chaoyi
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Kan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Centre for Computational and Evolutionary Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiudeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Weini
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Shanming
authors.initials: S
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Centre for Computational and Evolutionary Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Shian
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang, Beijing 100101, China.
authors.forename: Dahua
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010053:Ovary / Q000166:cytology* / Q000254:growth & development; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C092937:ci protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases