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Evidence that stem cells reside in the adult Drosophila midgut epithelium

Abstract

Adult stem cells maintain organ systems throughout the course of life and facilitate repair after injury or disease1. A fundamental property of stem and progenitor cell division is the capacity to retain a proliferative state or generate differentiated daughter cells2; however, little is currently known about signals that regulate the balance between these processes. Here, we characterize a proliferating cellular compartment in the adult Drosophila midgut. Using genetic mosaic analysis we demonstrate that differentiated cells in the epithelium arise from a common lineage. Furthermore, we show that reduction of Notch signalling leads to an increase in the number of midgut progenitor cells, whereas activation of the Notch pathway leads to a decrease in proliferation. Thus, the midgut progenitor's default state is proliferation, which is inhibited through the Notch signalling pathway. The ability to identify, manipulate and genetically trace cell lineages in the midgut should lead to the discovery of additional genes that regulate stem and progenitor cell biology in the gastrointestinal tract.

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Figure 1: Cellular organization of the adult Drosophila midgut epithelium.
Figure 2: Cell proliferation in the adult Drosophila midgut.
Figure 3: Cells of the midgut arise from a common lineage.
Figure 4: Notch pathway regulates the number of midgut progenitors.

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Acknowledgements

We thank GETDB and Bloomington stock centers for providing fly strains. C.A.M. would like to acknowledge colleagues in the Perrimon laboratory for many constructive discussions and criticisms; B. Mathey-Prevot for comments on the manuscript; K. Brückner for help in translating the seminal text by M. Strasburger from German; R. Binari for technical assistance; and S. Tang and C. Villata for help in screening. C.A.M. was supported by a NRSA fellowship and a grant from the Harvard Stem Cell Institute. N.P. is a HHMI investigator.

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Correspondence to Craig A. Micchelli.

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Supplementary information

Supplementary Figure Legends

Text to accompany Supplementary Figures 1–4. (DOC 20 kb)

Supplementary Figure 1

Whole mount adult Drosophila gastrointestinal tract imaged in cross-section. (PDF 17 kb)

Supplementary Figure 2

esg+ cells define a population of midgut progenitors. (PDF 14 kb)

Supplementary Figure 3

Gal80ts provides control of transgene expression in the adult midgut. (PDF 16 kb)

Supplementary Figure 4

A model of the adult Drosophila midgut. (PDF 17 kb)

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Micchelli, C., Perrimon, N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475–479 (2006). https://doi.org/10.1038/nature04371

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