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Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR‐8–Escargot switch
Author(s) -
Antonello Zeus A,
Reiff Tobias,
BallestaIllan Esther,
Dominguez Maria
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591517
Subject(s) - biology , microbiology and biotechnology , robustness (evolution) , progenitor cell , stem cell , progenitor , cellular differentiation , microrna , motility , gene , genetics
Abstract The intestinal epithelium is remarkably robust despite perturbations and demand uncertainty. Here, we investigate the basis of such robustness using novel tracing methods that allow simultaneously capturing the dynamics of stem and committed progenitor cells (called enteroblasts) and intestinal cell turnover with spatiotemporal resolution. We found that intestinal stem cells ( ISC s) divide “ahead” of demand during Drosophila midgut homeostasis. Their newborn enteroblasts, on the other hand, take on a highly polarized shape, acquire invasive properties and motility. They extend long membrane protrusions that make cell–cell contact with mature cells, while exercising a capacity to delay their final differentiation until a local demand materializes. This cellular plasticity is mechanistically linked to the epithelial–mesenchymal transition ( EMT ) programme mediated by escargot , a snail family gene. Activation of the conserved micro RNA miR‐8/miR‐200 in “pausing” enteroblasts in response to a local cell loss promotes timely terminal differentiation via a reverse MET by antagonizing escargot. Our findings unveil that robust intestinal renewal relies on hitherto unrecognized plasticity in enteroblasts and reveal their active role in sensing and/or responding to local demand.