Drosophila as a Model to Study Intestinal Stem Cells

Abstract

Although there were several old reports described proliferating stem‐like cells in adult intestinal tissue of insects, Drosophila digestive tract has not been drawing attention from intestinal stem cell (ISC) scientists. In 2006, two studies (Micchelli and Perrimon, 2006; Ohlstein and Spradling, 2006) revisited this issue. As they clearly pointed out active stem cell population in this organ and evidenced the usefulness of Drosophila digestive tract as an ideal model system to study ISCs, the fly intestine was finally brought into the light of stem cell science. Fly ISCs require multiple signals to maintain their proper function similar to their mammalian counterparts do. Notch, Wnt, JAK/STAT and EGFR signals are initially reported as the key players but many other genes and signals are also listed up to date. In this article, a landscape of the network comprised with a variety of signals and genes controlling ISC behaviour (i.e. self‐renewal, proliferation and differentiation) is observed.

Key Concepts

  • Drosophila intestinal stem cell (ISC) research provides essential ideas to understand how stem cells keep organ integrity throughout life.
  • Precision and robust regulation of ISC functions by a variety of signalling activities ensures constant tissue renewal and recovery from severe injury.
  • The functions of ISC include self‐renewal, proliferation, cell‐fate choice and differentiation into mature intestinal cells.
  • Each function is regulated by distinct molecular signals with multiple mutual interactions.
  • The aim of this article is to provide current knowledge about Drosophila ISCs and the idea how rapidly this research area expands using molecular genetics‐friendly Drosophila as a model organism.

Keywords: intestinal stem cell; Notch; Wnt; EGFR; JAK/STAT; BMP; Drosophila

Figure 1. Comparison of Drosophila midgut and mammalian intestine. ISCs are in orange, committed progeny in blue, differentiated cells in grey (absorptive) or in blue–grey (secretory) and nonepithelial visceral muscle (Drosophila) or stromal cells (mammalian) in dark‐grey. (a) ISCs are found on the basal side of the epithelium in Drosophila. (b) In mammalian crypt, ISCs reside at the bottom, squeezed between Paneth cells. Arrows indicate the direction of the cell movement. In both systems, cells migrate horizontally to the basement membrane (green). (c) A surface view of Drosophila midgut epithelium. ISCs and EBs are visualised by esg‐Gal4 driven UAS‐myrRFP (red). Cell nuclei are in blue.
Figure 2. Signals and genes controlling Drosophila midgut ISC and its lineage. (a) A number of signals and genes control homeostatic ISC behaviour. (b) In damaged condition by pathogenic infection or drug‐induced injury, ISC proliferation is strongly induced by multiple signals. The colour code is same as in Figure.
Figure 3. Development of the Drosophila midgut from embryo to adult. esg‐positive stem‐cell like population forms distinct gut epithelia in the embryonic, larval and pupal stages, respectively. Refer to the text for detail.
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Further Reading

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Vermeulen L and Snippert HJ (2014) Stem cell dynamics in homeostasis and cancer of the intestine. Nature Reviews Cancer 14: 468–480.

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Takashima, Shigeo(Nov 2015) Drosophila as a Model to Study Intestinal Stem Cells. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022526]