Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

Abstract

Adult tissue homeostasis requires a tight balance between the removal of old or damaged cells and the production of new ones. Such processes are usually driven by dedicated stem cells that reside within specific tissue locations or niches (Nystul and Spradling, 2006).The intestinal epithelium has a remarkable regenerative capacity, which has made it a prime paradigm for the study of stem cell-driven tissue self-renewal. The discovery of the presence of stem cells in the adult midgut of the fruit fly Drosophila melanogaster has significantly impacted our understanding of the role of stem cells in intestinal homeostasis. Here we will review the current knowledge of the main mechanisms involved in the regulation of tissue homeostasis in the adult Drosophila midgut, with a focus on the role of stem cells in this process. We will also discuss processes involving acute or chronic disruption of normal intestinal homeostasis such as damage-induced regeneration and ageing.3

Maintenance of the adult Drosophila intestine: all roads lead to homeostasis

“…In addition two layers of visceral muscle surround the midgut: an outer layer of longitudinal muscle and an inner layer of circular muscle [5]. The function of the visceral muscle is twofold; visceral muscle mediates intestinal peristalsis [6] and is an important source of signaling pathway ligands that regulate ISC proliferation [7-12]. …”

“…In the eight years since the identification of ISCs in the Drosophila midgut, a large body of literature has emerged demonstrating that midgut ISCs adjust their rates of proliferation in response to enterocyte turnover through a combination of positive and negative feedback loops initiated by enterocyte, enteroendocrine progenitor, visceral muscle, tracheal, and hemocyte derived signaling pathway ligands [7-12, 40-48]. These loops act in combination to link turnover of differentiated cells to both ISC division and enteroblast differentiation, thereby precisely and rapidly restoring tissue structure and function following loss of ECs and ee cells (Fig.…”

Intestinal regeneration as an insect resistance mechanism to entomopathogenic bacteria

“…In contrast to the four gut cell types of lepidopteran larvae, a fifth cell type named transient amplifying (TA) cells, appears only during pathogenic episodes in Drosophila . The gene expression profiles and intracellular regulators of ISCs have been described in-depth to ascertain the molecular characteristics defining the intestinal stem cell condition [33]. In Drosophila ISCs the proliferation or differentiation fate depend on an interaction between expression of nuclear binding transcription factors [33].…”

“…The gene expression profiles and intracellular regulators of ISCs have been described in-depth to ascertain the molecular characteristics defining the intestinal stem cell condition [33]. In Drosophila ISCs the proliferation or differentiation fate depend on an interaction between expression of nuclear binding transcription factors [33]. Another relevant factor in determining ISC fate in Drosophila is the directionality of ISC secretion and uptake.…”

Damage-Induced Cell Regeneration in the Midgut of Aedes albopictus Mosquitoes

“…Food digestion, ingestion of cytotoxic compounds, enteric infections and molecules produced during the immune response are major gut stress-inducers13. In Drosophila melanogaster , the presence of such stress-inducers in the gut lumen result in cell damage and loss of the absorptive and digestive enterocytes (ECs), the predominant cell type in the gut epithelium14. In order to compensate for the loss of ECs, the gut possesses protective homeostatic mechanisms relying on the activity of intestinal stem cells (ISCs) that are scattered along the midgut epithelium141516.…”