Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Evidence that stem cells reside in the adult Drosophila midgut epithelium


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.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. Radtke, F. & Clevers, H. Self-renewal and cancer of the gut: Two sides of a coin. Science 307, 1904–1909 (2005)

    ADS  CAS  Article  PubMed  Google Scholar 

  2. Molofsky, A. V., Pardal, R. & Morrison, S. J. Diverse mechanisms regulate stem cell self-renewal. Curr. Opin. Cell Biol. 16, 700–707 (2004)

    CAS  Article  PubMed  Google Scholar 

  3. Strasburger, M. Bau, Funktion und Variabilität des Darmtractus von Drosophila melanogaster Meigen. Zeit. f. wiss. Zool. 140, 539–649 (1932)

    Google Scholar 

  4. Wigglesworth, V. The Principles of Insect Physiology (Methuen & Co. Ltd, London, 1965)

    Google Scholar 

  5. Miller, A. in The Biology of Drosophila (ed. Demerec, M.) 420–442 (Hafner, New York, 1950)

    Google Scholar 

  6. Bozuck, A. N. DNA synthesis in the absence of somatic cell division associated with ageing in Drosophila subobscura. Exp. Geront. 7, 147–156 (1972)

    Article  Google Scholar 

  7. Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neural morphogenesis. Neuron 22, 451–461 (1999)

    CAS  Article  PubMed  Google Scholar 

  8. Xu, T. & Rubin, G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993)

    CAS  PubMed  Google Scholar 

  9. Furriols, M. & Bray, S. J. A model Notch response element detects Suppressor of Hairless dependent molecular switch. Curr. Biol. 11, 60–64 (2001)

    CAS  Article  PubMed  Google Scholar 

  10. Fuse, N., Hirose, S. & Hayashi, S. Diploidy of Drosophila imaginal cells is maintained by a transcriptional repressor encoded by escargot. Genes Dev. 8, 2270–2281 (1994)

    CAS  Article  PubMed  Google Scholar 

  11. Kiger, A., White-Cooper, H. & Fuller, M. T. Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407, 750–754 (2000)

    ADS  CAS  Article  PubMed  Google Scholar 

  12. McGuire, S. E. et al. Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302, 1765–1768 (2003)

    ADS  CAS  Article  PubMed  Google Scholar 

  13. Presente, A., Shaw, S., Nye, J. S. & Andres, A. J. Transgene-mediated RNA interference defines a novel role for Notch in chemosensory startle behaviour. Genesis 34, 165–169 (2002)

    CAS  Article  PubMed  Google Scholar 

  14. Ohlstein, B. & Spradling, A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature advance online publication, 7 December 2005 (doi:10.1038/nature04333).

  15. Torii, M. et al. Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system. Development 126, 443–456 (1999)

    CAS  PubMed  Google Scholar 

  16. Li, L. & Vaessin, H. Pan-neural prospero terminates cell proliferation during Drosophila neurogenesis. Genes Dev. 14, 147–151 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Schonhoff, S. E., Giel-Moloney, M. & Leiter, A. B. Minireview: Development and differentiation of gut endocrine cells. Endocrinology 145, 2639–2644 (2005)

    Article  Google Scholar 

  18. Xie, T. & Spradling, A. in Stem Cell Biology (eds Marshak, D. R., Gardner, R. L. & Gottlieb, D.) 129–148 (Cold Spring Harbor Press, New York, 2001)

    Google Scholar 

  19. Kiger, A. & Fuller, M. in Stem Cell Biology (eds Marshak, D. R, Gardner, R. L. & Gottlieb, D.) 149–187 (Cold Spring Harbor Press, New York, 2001)

    Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Craig A. Micchelli.

Ethics declarations

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Micchelli, C., Perrimon, N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475–479 (2006).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing