Using pathogens or high levels of opportunistic bacteria to damage the gut, studies in Drosophila have identified many signaling pathways involved in gut regeneration. Dying cells emit signaling molecules that accelerate intestinal stem cell proliferation and progenitor differentiation to replace the dying cells quickly. This process has been named ‘regenerative cell death’. Here, mimicking environmental conditions, we show that the ingestion of low levels of opportunistic bacteria was sufficient to launch an accelerated cellular renewal program despite the brief passage of bacteria in the gut and the absence of cell death and this is is due to the moderate induction of the JNK pathway that stimulates stem cell proliferation. Consequently, the addition of new differentiated cells to the gut epithelium, without preceding cell loss, leads to enterocyte overcrowding. Finally, we show that a couple of days later, the correct density of enterocytes is promptly restored by means of a wave of apoptosis involving Hippo signaling and preferential removal of old enterocytes.
The authors declare no competing or financial interests.
R.L. contributed to conception and design, acquisition of data, analysis and interpretation of data, revising the article; A.B.-B., O.B., M.-P.N.-E. and M.A. contributed to acquisition of data; D.P. contributed to acquisition of data and revising the article; A.G. contributed to conception and design, drafting and revising the article.
This work was supported by a grant from the MESR (Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche) (R.L.), the Fondation pour la Recherche Médicale (R.L.), the Institut National de la Recherche Agronomique, the Centre National de la Recherche Scientifique, and the Agence Nationale de la Recherche (ANR-13-CESA-0003-01 to A.G.).
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.142539.supplemental
- Received July 22, 2016.
- Accepted January 10, 2017.