Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size
Abstract
The gut is the primary interface between an animal and food, but how it adapts to qualitative dietary variation is poorly defined. We find that the Drosophila midgut plastically resizes following changes in dietary composition. A panel of nutrients collectively promote gut growth, which sugar opposes. Diet influences absolute and relative levels of enterocyte loss and stem cell proliferation, which together determine cell numbers. Diet also influences enterocyte size. A high sugar diet inhibits translation and uncouples ISC proliferation from expression of niche-derived signals but, surprisingly, rescuing these effects genetically was not sufficient to modify diet's impact on midgut size. However, when stem cell proliferation was deficient, diet's impact on enterocyte size was enhanced, and reducing enterocyte-autonomous TOR signaling was sufficient to attenuate diet-dependent midgut resizing. These data clarify the complex relationships between nutrition, epithelial dynamics, and cell size, and reveal a new mode of plastic, diet-dependent organ resizing.
Data availability
Data have been submitted with an ArrayExpress accession E-MTAB-10812.
Article and author information
Author details
Funding
National Institutes of Health (1R21AG065733-01,1R01AI148541-01A1)
- Alessandro Bonfini
- Jonathan Revah
- Xi Liu
- Philip Houtz
- Nicolas Buchon
National Science Foundation (IOS-1656118,IOS-1653021)
- Alessandro Bonfini
- Jonathan Revah
- Xi Liu
- Philip Houtz
- Nicolas Buchon
UK Research and Innovation (MR/S033939/1)
- Adam J Dobson
Agence Nationale de la Recherche (ANR-10-LABX-41; ANR-11-IDEX-0002-02)
- David Duneau
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lucy Erin O'Brien, Stanford University School of Medicine, United States
Version history
- Received: December 16, 2020
- Accepted: September 22, 2021
- Accepted Manuscript published: September 23, 2021 (version 1)
- Version of Record published: October 19, 2021 (version 2)
Copyright
© 2021, Bonfini 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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