Lola regulates Drosophila adult midgut homeostasis via non-canonical Hippo signaling

  1. Xue Hao
  2. Shimin Wang
  3. Yi Lu
  4. Wentao Yu
  5. Pengyue Li
  6. Dan Jiang
  7. Tong Guo
  8. Mengjie Li
  9. Jinhui Li
  10. Jinjin Xu
  11. Wenqing Wu
  12. Margaret S Ho  Is a corresponding author
  13. Lei Zhang  Is a corresponding author
  1. Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, China
  2. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
  3. School of Life Science and Biotechnology, The Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, China
  4. School of Life Science and Technology, ShanghaiTech University, China

Abstract

Tissue homeostasis and regeneration in the Drosophila midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation by sequestering the transcription co-factor Yorkie (Yki) in the cytoplasm, a factor required for rapid ISC proliferation under injury-induced regeneration. Nonetheless, the mechanism of Hippo-mediated midgut homeostasis and whether canonical Hippo signaling is involved in ISC basal proliferation are less characterized. Here we identify Lola as a transcription factor acting downstream of Hippo signaling to restrict ISC proliferation in a Yki-independent manner. Not only that Lola interacts with and is stabilized by the Hippo signaling core kinase Warts (Wts), Lola rescues the enhanced ISC proliferation upon Wts depletion via suppressing Dref and SkpA expressions. Our findings reveal that Lola is a non-canonical Hippo signaling component in regulating midgut homeostasis, providing insights on the mechanism of tissue maintenance and intestinal function.

Data availability

Sequencing data have been deposited in GEO under accession code GSE136999, and SRA under accession code SRP220236.All data generated or analysed during this study are included in the manuscript.

The following data sets were generated

Article and author information

Author details

  1. Xue Hao

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Shimin Wang

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yi Lu

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Wentao Yu

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Pengyue Li

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Dan Jiang

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Tong Guo

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Mengjie Li

    State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, The Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Jinhui Li

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Jinjin Xu

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Wenqing Wu

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Margaret S Ho

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    For correspondence
    margareth@shanghaitech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2387-7564
  13. Lei Zhang

    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    rayzhang@sibcb.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2566-6493

Funding

Chinese Academy of Sciences (Strategic Priority Research Program XDB19000000)

  • Lei Zhang

National Natural Science Foundation of China (No. 31530043)

  • Lei Zhang

National Natural Science Foundation of China (No. 31625017)

  • Lei Zhang

National Natural Science Foundation of China (No. 31871039)

  • Margaret S Ho

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kathryn Song Eng Cheah, The University of Hong Kong, Hong Kong

Publication history

  1. Received: April 9, 2019
  2. Accepted: January 10, 2020
  3. Accepted Manuscript published: January 14, 2020 (version 1)
  4. Version of Record published: January 24, 2020 (version 2)

Copyright

© 2020, Hao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xue Hao
  2. Shimin Wang
  3. Yi Lu
  4. Wentao Yu
  5. Pengyue Li
  6. Dan Jiang
  7. Tong Guo
  8. Mengjie Li
  9. Jinhui Li
  10. Jinjin Xu
  11. Wenqing Wu
  12. Margaret S Ho
  13. Lei Zhang
(2020)
Lola regulates Drosophila adult midgut homeostasis via non-canonical Hippo signaling
eLife 9:e47542.
https://doi.org/10.7554/eLife.47542

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