Lola regulates Drosophila adult midgut homeostasis via non-canonical Hippo signaling
- Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, China
- Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
- School of Life Science and Biotechnology, The Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, China
- 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.
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Genome-wide binding of Lola in S2 cellsNCBI Gene Expression Omnibus, GSE136999.
Article and author information
Author details
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
- Kathryn Song Eng Cheah, The University of Hong Kong, Hong Kong
Version history
- Received: April 9, 2019
- Accepted: January 10, 2020
- Accepted Manuscript published: January 14, 2020 (version 1)
- 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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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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