The Drosophila posterior midgut is closely analogous to the mammalian small intestine; the midgut epithelium is maintained by frequent division of self-renewing intestinal stem cells (ISCs). This system has been extensively characterized in the context of general models of epithelial homeostasis. Developmental signals and signaling pathways, including signaling within the local microenvironment, have been characterized.
Development of differentiated absorptive and secretory gut cell types requires Notch signaling; loss of Notch (N) function in the posterior midgut results in stem cell tumor formation. This system has been exploited by using targeted RNAi-effected loss of N expression in the ISCs to investigate triggers for and downstream effectors of stem cell tumorigenesis. See Singh et al., 2019 (FBrf0243415), for a recent review and summary.
Up to 10% of aged wild-type males are found to have at least one stem-cell tumor in the gut. Since N is sex-linked, Drosophila males are susceptible to effects of spontaneous somatic loss of the N gene. Many of the spontaneous tumors were shown to have genetic lesions that affected the Notch region.
Drosophila adult stem cells have been found to be resistant to radiation- or chemical-induced apoptosis, thus providing a means to investigate mechanisms of resistance of stem cell tumors to various anticancer therapies.
This system has been used to characterize regulation of mitochondrial pyruvate metabolism in stem cell maintenance and differentiation and the role of Dmel\Mpc1 (ortholog of human MPC1) in that process.
The intestinal stem cell model has also been used to study colorectal cancer, by expressing implicated genes or gene variants in ISCs. See human disease model reports listed in "Related Diseases" section, below, for additional models based on this system.
[updated Oct. 2019 by FlyBase; FBrf0222196]