A stress-responsive miRNA regulates BMP signaling to maintain tissue homeostasis.

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, <i>miR-958</i>, that non-cell autonomously regulates stem cell numbers during tissue homeostasis and regeneration in the <i>Drosophila</i> adult midgut. We identify its downstream target <i>cabut</i>, the <i>Drosophila</i> ortholog of mammalian KLF10/11 transcription factors, which mediates this <i>miR-958</i> function by promoting paracrine enterocyte-to-stem-cell bone morphogenetic protein (BMP) signaling. We also show that mature <i>miR-958</i> 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 <i>Drosophila</i> adult intestinal tissue during both normal homeostasis and tissue regeneration to regulate intestinal stem cell numbers.