Open Close
General Information
Name
cancer, intestinal stem cell models
FlyBase ID
FBhh0000767
Disease Ontology Term
Parent Disease
OMIM
Overview

The Drosophila posterior midgut is closely analogous to the mammalian small intestine; the midgut epithelium is maintained by frequent division of self-renewing intestinal stem cells (ISCs). This system has been extensively characterized in the context of general models of epithelial homeostasis. Developmental signals and signaling pathways, including signaling within the local microenvironment, have been characterized.

Development of differentiated absorptive and secretory gut cell types requires Notch signaling; loss of Notch (N) function in the posterior midgut results in stem cell tumor formation. This system has been exploited by using targeted RNAi-effected loss of N expression in the ISCs to investigate triggers for and downstream effectors of stem cell tumorigenesis. See Singh et al., 2019 (FBrf0243415), for a recent review and summary.

Up to 10% of aged wild-type males are found to have at least one stem-cell tumor in the gut. Since N is sex-linked, Drosophila males are susceptible to effects of spontaneous somatic loss of the N gene. Many of the spontaneous tumors were shown to have genetic lesions that affected the Notch region.

Drosophila adult stem cells have been found to be resistant to radiation- or chemical-induced apoptosis, thus providing a means to investigate mechanisms of resistance of stem cell tumors to various anticancer therapies.

This system has been used to characterize regulation of mitochondrial pyruvate metabolism in stem cell maintenance and differentiation and the role of Dmel\Mpc1 (ortholog of human MPC1) in that process.

The intestinal stem cell model has also been used to study colorectal cancer, by expressing implicated genes or gene variants in ISCs. See human disease model reports listed in "Related Diseases" section, below, for additional models based on this system.

[updated Oct. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, intestinal stem cell models
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
intestinal cancer
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate- to high-scoring ortholog of human NOTCH1, NOTCH2, NOTCH3, NOTCH4 (1 Drosophila to 4 human). Dmel\N shares 43-44% identity and 56-57% similarity with NOTCH1 and NOTCH2.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (50 groups)
      protein-protein
      Interacting group
      Assay
      References
      two hybrid, electron microscopy, molecular weight, enzyme linked immunosorbent assay
      anti tag coimmunoprecipitation, anti tag western blot, western blot
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      pull down, western blot
      experimental knowledge based
      pull down, western blot, anti tag coimmunoprecipitation
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, autoradiography, two hybrid
      proximity ligation assay, fluorescence microscopy
      affinity technology, tag visualisation by alkaline phosphatase activity
      anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, pull down, autoradiography
      affinity technology, tag visualisation by alkaline phosphatase activity, pull down, inferred by author, fluorescence microscopy, bead aggregation assay, anti bait coimmunoprecipitation, western blot, enzyme linked immunosorbent assay, tag visualisation, atomic force microscopy, phenotype-based detection assay
      pull down, western blot, anti bait coimmunoprecipitation, two hybrid, autoradiography
      two hybrid, anti tag coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, anti tag western blot, two hybrid, anti tag coimmunoprecipitation, western blot
      pull down, western blot, two hybrid, anti tag coimmunoprecipitation
      protease assay, western blot, inferred by author
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting, protein three hybrid, three hybrid
      pull down, western blot
      pull down, western blot
      pull down, western blot
      coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot, pull down
      two hybrid, pull down, autoradiography
      anti tag coimmunoprecipitation, western blot, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot
      inferred by author, confocal microscopy, bead aggregation assay, affinity technology, tag visualisation by alkaline phosphatase activity, pull down, tag visualisation, anti tag coimmunoprecipitation, western blot, fluorescence microscopy
      anti bait coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot, pull down, anti tag western blot, anti tag coimmunoprecipitation
      nuclear magnetic resonance, pull down, molecular weight estimation by staining, autoradiography, western blot, isothermal titration calorimetry, predetermined participant
      anti bait coimmunoprecipitation, anti tag western blot, western blot, pull down, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, protein three hybrid, isothermal titration calorimetry, predetermined participant, coimmunoprecipitation, cosedimentation, molecular sieving, molecular weight estimation by staining, electrophoretic mobility shift assay, electrophoretic mobility supershift assay, electron microscopy, three hybrid
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot, pull down, two hybrid
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      inferred by author, confocal microscopy, bead aggregation assay
      RNA-protein
      Interacting group
      Assay
      References
      nucleic acid uv cross-linking assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
      pull down, quantitative reverse transcription pcr
      Alleles Reported to Model Human Disease (Disease Ontology) (10 alleles)
      Models Based on Experimental Evidence ( 4 )
      Modifiers Based on Experimental Evidence ( 9 )
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - genetic evidence
      P-element activity
      loss of function allele
      spontaneous
      loss of function allele
      spontaneous
      amorphic allele - genetic evidence
      X ray
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      gamma ray
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      X ray
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      loss of function allele
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      X ray
      amorphic allele - genetic evidence
      loss of function allele
      spontaneous
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      X ray
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      References (35)