The adult Drosophila posterior midgut is maintained by pluripotent stem cells

Vertebrate and invertebrate digestive systems show extensive similarities in their development, cellular makeup and genetic control. The Drosophila midgut is typical: enterocytes make up the majority of the intestinal epithelial monolayer, but are interspersed with hormone-producing enteroendocrine cells. Human (and mouse) intestinal cells are continuously replenished by stem cells, the misregulation of which may underlie some common digestive diseases and cancer. In contrast, stem cells have not been described in the intestines of flies, and Drosophila intestinal cells have been thought to be relatively stable. Here we use lineage labelling to show that adult Drosophila posterior midgut cells are continuously replenished by a distinctive population of intestinal stem cells (ISCs). As in vertebrates, ISCs are multipotent, and Notch signalling is required to produce an appropriate fraction of enteroendocrine cells. Notch is also required for the differentiation of ISC daughter cells, a role that has not been addressed in vertebrates. Unlike previously characterized stem cells, which reside in niches containing a specific partner stromal cell, ISCs adjoin only the basement membrane, differentiated enterocytes and their most recent daughters. The identification of Drosophila intestinal stem cells with striking similarities to their vertebrate counterparts will facilitate the genetic analysis of normal and abnormal intestinal function.

[1]  R. Powning,et al.  A Study of the Processes of Digestion in Certain Insects , 1949 .

[2]  A. Spradling,et al.  A Balbiani body and the fusome mediate mitochondrial inheritance during Drosophila oogenesis , 2003, Development.

[3]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[4]  A. Spradling,et al.  Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. , 2001, Developmental biology.

[5]  D. Stainier No Organ Left Behind: Tales of Gut Development and Evolution , 2005, Science.

[6]  A. Spradling,et al.  Identification and behavior of epithelial stem cells in the Drosophila ovary. , 1995, Development.

[7]  B. Stay,et al.  Immunocytochemical localization of Diploptera punctata allatostatin‐like peptide in Drosophila melanogaster , 1995, The Journal of comparative neurology.

[8]  E. Fuchs,et al.  Socializing with the Neighbors Stem Cells and Their Niche , 2004, Cell.

[9]  A. D. Imms,et al.  Principles of Insect Morphology , 1935, Nature.

[10]  A. Spradling,et al.  The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. , 2005, Developmental cell.

[11]  D. Coates,et al.  Expression and Functional Characterization of aDrosophila Neuropeptide Precursor with Homology to Mammalian Preprotachykinin A* , 2000, The Journal of Biological Chemistry.

[12]  F L STONE,et al.  TWO SIDES OF THE COIN. , 1963, Journal of medical education.

[13]  A. Spradling,et al.  The Drosophila endocycle is controlled by Cyclin E and lacks a checkpoint ensuring S-phase completion. , 1996, Genes & development.

[14]  M. Demerec,et al.  Biology of Drosophila , 1950 .

[15]  D. Nässel Tachykinin-related peptides in invertebrates: a review , 1999, Peptides.

[16]  Susan E. Schonhoff,et al.  Minireview: Development and differentiation of gut endocrine cells. , 2004, Endocrinology.

[17]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[18]  N. Perrimon,et al.  Evidence that stem cells reside in the adult Drosophila midgut epithelium , 2006, Nature.

[19]  L. P. Gartner Submicroscopic morphology of the adult drosophila midgut. , 1970, Journal of the Baltimore College of Dental Surgery.

[20]  R. Hakim,et al.  Growth and differentiation of the larval midgut epithelium during molting in the moth, Manduca sexta. , 1991, Tissue & cell.

[21]  S. Andersson,et al.  RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila. , 1994, Development.

[22]  A. Spradling,et al.  The stem cell niche: theme and variations. , 2004, Current opinion in cell biology.

[23]  E. Wieschaus,et al.  Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless , 1990, Cell.

[24]  Hans Clevers,et al.  Self-Renewal and Cancer of the Gut: Two Sides of a Coin , 2005, Science.

[25]  O. Baumann Posterior midgut epithelial cells differ in their organization of the membrane skeleton from other drosophila epithelia. , 2001, Experimental cell research.

[26]  R. Snodgrass,et al.  Principles of Insect Morphology , 1993 .

[27]  L. P. Gartner Ultrastructural examination of ageing and radiation-induced life-span shortening in adult Drosophila melanogaster. , 1973, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[28]  Joseph Haydn,et al.  A Theme and Variations , 1956 .

[29]  N. Perrimon,et al.  Simple and efficient generation of marked clones in Drosophila , 1993, Current Biology.

[30]  N. Perrimon,et al.  γ‐Secretase/presenilin inhibitors for Alzheimer's disease phenocopy Notch mutations in Drosophila , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  F. Kafatos,et al.  Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes , 2000, The EMBO journal.

[32]  S. Tobe,et al.  Allatostatins: A Growing Family of Neuropeptides with Structural and Functional Diversity , 1999, Annals of the New York Academy of Sciences.

[33]  J. Mohler,et al.  Temperature-sensitive mutations of the notch locus in Drosophila melanogaster. , 1975, Genetics.