A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration
Abstract Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55255-1 |
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| author | Dan Jiang Pengyue Li Yi Lu Jiaxin Tao Xue Hao Xiaodong Wang Wei Wu Jinjin Xu Haoen Zhang Xiaoyu Li Yixing Chen Yunyun Jin Lei Zhang |
| author_facet | Dan Jiang Pengyue Li Yi Lu Jiaxin Tao Xue Hao Xiaodong Wang Wei Wu Jinjin Xu Haoen Zhang Xiaoyu Li Yixing Chen Yunyun Jin Lei Zhang |
| author_sort | Dan Jiang |
| collection | DOAJ |
| description | Abstract Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs). Mechanistically, our findings demonstrate that Pax is a conserved target gene of the Hippo signaling pathway in both Drosophila and mammals. Subsequent investigations have revealed Pax interacts with Yki and enhances its cytoplasmic localization, thereby establishing a feedback regulatory mechanism that attenuates Yki activity and ultimately inhibits ISCs proliferation. Additionally, Pax induces the differentiation of ISCs into ECs by activating Notch expression, thus facilitating the differentiation process. Overall, our study highlights Pax as a pivotal component of the Hippo and Notch pathways in regulating midgut homeostasis, shedding light on this growth-related pathway in tissue maintenance and intestinal function. |
| format | Article |
| id | doaj-art-a7cce1fe8b2b4f509264e46ce68c34d7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-a7cce1fe8b2b4f509264e46ce68c34d72025-01-12T12:30:58ZengNature PortfolioNature Communications2041-17232025-01-0116112110.1038/s41467-024-55255-1A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regenerationDan Jiang0Pengyue Li1Yi Lu2Jiaxin Tao3Xue Hao4Xiaodong Wang5Wei Wu6Jinjin Xu7Haoen Zhang8Xiaoyu Li9Yixing Chen10Yunyun Jin11Lei Zhang12The Department of Urology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesSchool of Life Science and Technology, ShanghaiTech UniversityState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesSheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of SciencesSheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityThe Department of Urology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityAbstract Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs). Mechanistically, our findings demonstrate that Pax is a conserved target gene of the Hippo signaling pathway in both Drosophila and mammals. Subsequent investigations have revealed Pax interacts with Yki and enhances its cytoplasmic localization, thereby establishing a feedback regulatory mechanism that attenuates Yki activity and ultimately inhibits ISCs proliferation. Additionally, Pax induces the differentiation of ISCs into ECs by activating Notch expression, thus facilitating the differentiation process. Overall, our study highlights Pax as a pivotal component of the Hippo and Notch pathways in regulating midgut homeostasis, shedding light on this growth-related pathway in tissue maintenance and intestinal function.https://doi.org/10.1038/s41467-024-55255-1 |
| spellingShingle | Dan Jiang Pengyue Li Yi Lu Jiaxin Tao Xue Hao Xiaodong Wang Wei Wu Jinjin Xu Haoen Zhang Xiaoyu Li Yixing Chen Yunyun Jin Lei Zhang A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration Nature Communications |
| title | A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration |
| title_full | A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration |
| title_fullStr | A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration |
| title_full_unstemmed | A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration |
| title_short | A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration |
| title_sort | feedback loop between paxillin and yorkie sustains drosophila intestinal homeostasis and regeneration |
| url | https://doi.org/10.1038/s41467-024-55255-1 |
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