Abstract
Adult organisms must sense and adapt to environmental fluctuations. In high-turnover tissues such as the intestine, these adaptive responses require rapid changes in gene expression that, in turn, likely involve posttranscriptional gene control. However, intestinal-tissue–specific microRNA (miRNA)-mediated regulatory pathways remain unexplored. Here, we report the role of an intestinal-specific miRNA, miR-958, that non–cell autonomously regulates stem cell numbers during tissue homeostasis and regeneration in the Drosophila adult midgut. We identify its downstream target cabut, the Drosophila ortholog of mammalian KLF10/11 transcription factors, which mediates this miR-958 function by promoting paracrine enterocyte-to-stem-cell bone morphogenetic protein (BMP) signaling. We also show that mature miR-958 levels transiently decrease in response to stress and that this decrease is required for proper stem cell expansion during tissue regeneration. In summary, we have identified a posttranscriptional mechanism that modulates BMP signaling activity within Drosophila adult intestinal tissue during both normal homeostasis and tissue regeneration to regulate intestinal stem cell numbers.
Funder
HHS | NIH | National Institute of General Medical Sciences
Publisher
Proceedings of the National Academy of Sciences
Cited by
13 articles.
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