Investigation of Tissue Homeostasis in the Drosophila Midgut

Abstract

Most tissues of multicellular organisms undergo cell turnovers in the adult stages. The questions of tissue homeostasis, i.e. how a tissue maintain a relatively stable number of cells, are critical for our understanding of wound healing, degenerative diseases, and tumorigenesis. The Drosophila midgut provides an excellent genetic model for studying tissue homeostasis in a simple epithelium. Similar to the mammalian gastrointestinal tract, the adult midgut of Drosophila harbors intestinal stem cells (ISCs), which can self-renew and produce differentiated cells such as the enterocytes (ECs) and enteroendocrine cells (EEs). ISCs are required for cell proliferation and tissue repair in the adult midgut. Strikingly, the pool size and proliferation/differentiation activity of ISCs can change dramatically under different physiological or pathological conditions in order to adjust to the regenerative demands. In order to understand how ISC activity and tissue homeostasis are regulated in the adult midgut, we performed an in vivo RNAi screen among genes encoding receptors or transmembrane proteins. A further characterization of top candidates in the screen has led to surprising discoveries about how ISCs sense their microenvironment, how ISCs coordinate the activity of major signaling pathways controlling proliferation and differentiation, and how tissue stress is connected with intracellular phosphate concentrations. Here I will present our findings and discuss how they have improved our knowledge about tissue homeostasis.