Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size

Bonfini, A., Dobson, A. J. , Duneau, D., Revah, J., Liu, X., Houtz, P. and Buchon, N. (2021) Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size. eLife, 10, e64125. (doi: 10.7554/elife.64125) (PMID:34553686) (PMCID:PMC8528489)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dobson, Dr Adam
Creator Roles:
Dobson, A. J.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review and editing
Authors: Bonfini, A., Dobson, A. J., Duneau, D., Revah, J., Liu, X., Houtz, P., and Buchon, N.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2021 Bonfini et al.
First Published:First published in eLife 10: e64125
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305846Remote control: How do microbiota promote animal health?Adam DobsonMedical Research Council (MRC)MR/S033939/1Institute of Molecular, Cell & Systems Biology