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General Information
Name
cancer, neural stem cell, disruption of asymmetric division
FlyBase ID
FBhh0000954
Disease Ontology Term
Parent Disease
OMIM
Overview

Asymmetric division is a critical step in the differentiation of post-embryonic stem cells during which each stem cell generates one self-renewing and one differentiating daughter cell. Mutations in Drosophila genes that disrupt the process of asymmetric division have been studied as models of neural-stem-cell derived cancers. Genes studied include numb, mira, pros, pins, brat, and l(3)mbt.

Loss-of-function mutations that affect normal neuroblast differentiation in Drosophila often result in conspicuous phenotypes of overproliferation and tumorous expansion of the brain at the larval stage. In brat or pros mutants, both daughter cells of the normally asymmetric division grow and behave like neuroblasts, leading to the formation of larval brain tumors comprised primarily of neuroblast-like cells. A sensitive test of neoplastic transformation is transplantation of potential tumorous cells into the abdomen of adult hosts; cells are observed for proliferation and invasive behaviors. One of the earliest genes characterized in this transplantation assay was brat. Homozygous loss-of-function mutations of numb, mira, pros, and pins have also been tested in this assay; larval brain tissue carrying neuroblasts with any of these mutations grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. The tumors became immortal and could be re-transplanted into new hosts for years.

See also reports for well-studied disease models using specific genes, 'cancer, neural stem cell, TRIM2,3-related' (FBhh0000772, using the fly gene brat) and 'cancer, neural stem cell, L3MBTL-related' (FBhh0000773, using the fly gene l(3)mbt).

[updated Jan. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, neural stem cell, disruption of asymmetric division
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
    Disease synonyms
    Search term: neoplastic phenotype(s)
    Search term: metastatic phenotype(s)
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (6)
        Gene Snapshot
        numb (numb) encodes a membrane-associated inhibitor of Notch signaling. It controls neuroblast and sense organ precursor asymmetric division. It is asymmetrically localized during mitosis and segregates exclusively to one of two daughter cells. [Date last reviewed: 2019-03-14]
        Molecular function (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        High-scoring ortholog of human NUMB and NUMBL (1 Drosophila to 2 human). Dmel\numb shares 39-41% identity and 49-51% similarity with the human genes.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Gene Snapshot
        miranda (mira) encodes a cytoplasmic and cortical scaffolding protein that binds the products of pros, stau and brat. It is asymmetrically localized to the basal cortex during neuroblast asymmetric cell division, resulting in its partioning into GMC daughter cells, where it is degraded and releases its cargo proteins. [Date last reviewed: 2019-03-14]
        Molecular function (GO)
        Gene Groups / Pathways
          Comments on ortholog(s)

          No gene orthologous to mira has been identified in human.

          Orthologs and Alignments from DRSC
          DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
          Gene Snapshot
          prospero (pros) encodes a protein that promotes the expression of neural differentiation genes and represses neuroblast stem cell identity genes and cell cycle proliferation genes; it is also important for astrocyte development. The product of pros is asymmetrically localized to the basal cortex during neuroblast asymmetric cell division, resulting in its partioning into GMC daughter cells, where it translocates into the nucleus. [Date last reviewed: 2019-03-14]
          Gene Groups / Pathways
          Comments on ortholog(s)

          Moderate-scoring ortholog of human PROX1 and PROX2 (1 Drosophila to 2 human). Dmel\pros shares 24-29% identity and 35-41% similarity with the human genes.

          Orthologs and Alignments from DRSC
          DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
          Gene Snapshot
          partner of inscuteable (pins) encodes a GDP-dissociation inhibitor involved in asymmetric cell division and mitotic spindle orientation. [Date last reviewed: 2019-06-13]
          Cellular component (GO)
          Gene Groups / Pathways
            Comments on ortholog(s)

            High-scoring ortholog of human GPSM2 and GPMS1 (1 Drosophila to 2 human). Dmel\pins shares 45-47% identity and 60-63% similarity with the human genes.

            Orthologs and Alignments from DRSC
            DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
            Gene Snapshot
            brain tumor (brat) encodes a tumor suppressor that regulates proliferation in the brain. During neural stem cell division, it segregates into one daughter cell where it inhibits protein translation, preventing self-renewal and inducing differentiation. It also acts during oogenesis where it interacts with the products of nos and pum to suppress hb translation. [Date last reviewed: 2019-03-07]
            Gene Groups / Pathways
              Comments on ortholog(s)

              Low-scoring ortholog of human TRIM3 and TRIM2 (2 Drosophila to 2 human). Dmel\brat shares 23-25% identity and 39-41% similarity with the human genes.

              Orthologs and Alignments from DRSC
              DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
              Gene Snapshot
              lethal (3) malignant brain tumor (l(3)mbt) encodes a tumor suppressor protein regulating proliferation in the brain, particularly the optic lobes. The proposed functions of the product of l(3)mbt include histone compaction, establishment of chromatin insulators, regulation of the Hippo pathway and repression of the germ line program in somatic cells. [Date last reviewed: 2019-09-26]
              Gene Groups / Pathways
                Comments on ortholog(s)

                Moderate-scoring ortholog of human L3MBTL3, L3MBTL4, and L3MBTL1 (1 Drosophila to 3 human). Dmel\l(3)mbt shares 28-31% identity and 42-46% similarity with the human genes.

                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 (98 groups)
                protein-protein
                Interacting group
                Assay
                References
                anti tag coimmunoprecipitation, anti tag western blot
                anti tag coimmunoprecipitation, western blot
                anti tag coimmunoprecipitation, western blot, pull down, anti bait coimmunoprecipitation, autoradiography, anti tag western blot
                pull down, western blot
                pull down, western blot
                anti tag coimmunoprecipitation, anti tag western blot
                pull down, western blot
                anti tag coimmunoprecipitation, anti tag western blot
                pull down, western blot, two hybrid
                pull down, autoradiography
                lambda phage display, pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, fluorescence polarization spectroscopy, predetermined participant
                two hybrid, pull down, autoradiography
                pull down, autoradiography, two hybrid, anti tag coimmunoprecipitation, western blot, molecular weight estimation by staining, cosedimentation, molecular weight, fluorescence polarization spectroscopy, predetermined participant, nuclear magnetic resonance
                pull down, western blot
                phage display, tag visualisation, pull down, anti tag western blot
                anti tag coimmunoprecipitation, western blot, anti tag western blot, x-ray crystallography, isothermal titration calorimetry, predetermined participant, pull down, molecular weight estimation by staining, two hybrid, cosedimentation, molecular weight, anti bait coimmunoprecipitation
                anti tag coimmunoprecipitation, anti tag western blot, western blot, anti bait coimmunoprecipitation
                RNA-RNA
                Interacting group
                Assay
                References
                luminiscence technology, necessary binding region
                protein-protein
                Interacting group
                Assay
                References
                protein cross-linking with a bifunctional reagent, molecular weight estimation by staining, detection by mass spectrometry, anti tag coimmunoprecipitation, western blot, comigration in gel electrophoresis
                pull down, western blot, enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
                pull down, anti tag western blot
                molecular sieving, molecular weight estimation by staining, two hybrid, isothermal titration calorimetry, predetermined participant, pull down, anti tag coimmunoprecipitation, anti tag western blot
                two hybrid, pull down, western blot
                anti tag coimmunoprecipitation, western blot, two hybrid
                pull down, autoradiography
                anti bait coimmunoprecipitation, peptide massfingerprinting, pull down, anti tag western blot, autoradiography, western blot
                pull down, autoradiography
                pull down, western blot
                anti tag coimmunoprecipitation, western blot
                anti bait coimmunoprecipitation, two hybrid, western blot, pull down, autoradiography
                anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, pull down, autoradiography, two hybrid, molecular sieving, x-ray crystallography, anti tag coimmunoprecipitation, anti tag western blot
                anti bait coimmunoprecipitation, peptide massfingerprinting
                RNA-protein
                Interacting group
                Assay
                References
                protein cross-linking with a bifunctional reagent, molecular weight estimation by staining, detection by mass spectrometry, anti tag coimmunoprecipitation, western blot, comigration in gel electrophoresis
                anti bait coimmunoprecipitation, two hybrid, western blot, pull down, autoradiography
                RNA-protein
                Interacting group
                Assay
                References
                pull down, Identification by mass spectrometry
                pull down, Identification by mass spectrometry
                anti bait coimmunoprecipitation, two hybrid, western blot, pull down, autoradiography
                pull down, autoradiography, anti tag coimmunoprecipitation, partial DNA sequence identification by hybridization, anti bait coimmunoprecipitation
                anti bait coimmunoprecipitation, quantitative reverse transcription pcr
                protein-protein
                Interacting group
                Assay
                References
                anti tag coimmunoprecipitation, anti tag western blot
                bimolecular fluorescence complementation, fluorescence microscopy
                two hybrid, pull down, autoradiography
                anti tag coimmunoprecipitation, western blot
                anti bait coimmunoprecipitation, two hybrid, western blot, pull down, autoradiography
                anti bait coimmunoprecipitation, western blot
                protein-protein
                Interacting group
                Assay
                References
                enzymatic study, autoradiography
                anti tag coimmunoprecipitation, peptide massfingerprinting
                anti bait coimmunoprecipitation, western blot, pull down
                anti bait coimmunoprecipitation, western blot, pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, two hybrid, anti tag western blot
                anti tag coimmunoprecipitation, peptide massfingerprinting
                anti tag coimmunoprecipitation, peptide massfingerprinting
                two hybrid, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down, autoradiography
                anti tag coimmunoprecipitation, western blot, fluorescent resonance energy transfer, experimental knowledge based, pull down, anti bait coimmunoprecipitation, two hybrid, autoradiography
                anti tag coimmunoprecipitation, Identification by mass spectrometry
                anti bait coimmunoprecipitation, western blot, two hybrid, x-ray crystallography, static light scattering, molecular weight, anti tag coimmunoprecipitation, pull down, molecular weight estimation by staining, molecular sieving, autoradiography, peptide massfingerprinting
                anti bait coimmunoprecipitation, western blot
                pull down, autoradiography, molecular sieving, molecular weight estimation by staining, anti tag coimmunoprecipitation, anti tag western blot, molecular weight estimation by coomasie staining, anti bait coimmunoprecipitation, western blot, coimmunoprecipitation, fluorescence polarization spectroscopy, predetermined participant, molecular weight estimation by silver staining, Identification by mass spectrometry
                anti tag coimmunoprecipitation, peptide massfingerprinting
                experimental knowledge based
                anti bait coimmunoprecipitation, western blot, pull down
                anti tag coimmunoprecipitation, Identification by mass spectrometry
                protein-protein
                Interacting group
                Assay
                References
                x-ray crystallography
                anti bait coimmunoprecipitation, western blot, two hybrid, anti tag coimmunoprecipitation, anti tag western blot, bimolecular fluorescence complementation, fluorescence microscopy, peptide massfingerprinting
                bimolecular fluorescence complementation, fluorescence microscopy, two hybrid, anti tag coimmunoprecipitation, anti tag western blot
                anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot
                molecular sieving, molecular weight estimation by staining, two hybrid, isothermal titration calorimetry, predetermined participant, pull down, anti tag coimmunoprecipitation, anti tag western blot
                pull down, western blot, anti tag western blot, three hybrid, molecular sieving, molecular weight estimation by staining, transcriptional complementation assay
                anti tag coimmunoprecipitation, peptide massfingerprinting
                pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, primer specific pcr
                two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot
                anti tag coimmunoprecipitation, anti tag western blot
                RNA-protein
                Interacting group
                Assay
                References
                iclip, partial RNA sequence identification
                anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, primer specific pcr, electrophoretic mobility shift assay, autoradiography
                anti bait coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, quantitative reverse transcription pcr, molecular sieving, static light scattering, nucleic acid uv cross-linking assay, Identification by mass spectrometry, microscale thermophoresis, predetermined participant, electrophoretic mobility shift assay, autoradiography
                electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr
                electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, quantitative reverse transcription pcr
                anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, primer specific pcr
                anti bait coimmunoprecipitation, northern blot
                anti tag coimmunoprecipitation, primer specific pcr
                pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, primer specific pcr
                anti tag coimmunoprecipitation, primer specific pcr
                electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
                protein-protein
                Interacting group
                Assay
                References
                anti tag coimmunoprecipitation, peptide massfingerprinting
                anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
                anti tag coimmunoprecipitation, western blot, molecular sieving, ion exchange chromatography, anti bait coimmunoprecipitation, Identification by mass spectrometry
                anti tag coimmunoprecipitation, western blot
                coimmunoprecipitation, western blot
                pull down, western blot
                affinity technology, peptide massfingerprinting, anti tag coimmunoprecipitation, western blot, pull down, autoradiography, molecular sieving, ion exchange chromatography, anti bait coimmunoprecipitation, experimental knowledge based
                pull down, autoradiography
                tandem affinity purification, Identification by mass spectrometry
                pull down, autoradiography
                Alleles Reported to Model Human Disease (Disease Ontology) (7 alleles)
                Models Based on Experimental Evidence ( 0 )
                Allele
                Disease
                Evidence
                References
                Modifiers Based on Experimental Evidence ( 1 )
                Allele
                Disease
                Interaction
                References
                Models Based on Experimental Evidence ( 0 )
                Allele
                Disease
                Evidence
                References
                Modifiers Based on Experimental Evidence ( 1 )
                Models Based on Experimental Evidence ( 1 )
                Allele
                Disease
                Evidence
                References
                Modifiers Based on Experimental Evidence ( 3 )
                Models Based on Experimental Evidence ( 1 )
                Allele
                Disease
                Evidence
                References
                Modifiers Based on Experimental Evidence ( 1 )
                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
                PM hybrid dysgenesis
                amorphic allele - genetic evidence
                diepoxybutane
                loss of function allele
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                diepoxybutane
                ethyl methanesulfonate
                amorphic allele - molecular evidence
                formaldehyde
                amorphic allele - molecular evidence
                ethyl methanesulfonate
                amorphic allele - molecular evidence
                ethyl methanesulfonate
                loss of function allele
                cre recombinase
                loss of function allele
                ethyl methanesulfonate
                loss of function allele
                ethyl methanesulfonate
                ethyl methanesulfonate
                amorphic allele - molecular evidence
                Delta2-3 transposase
                loss of function allele
                Delta2-3 transposase
                amorphic allele - molecular evidence
                Delta2-3 transposase
                loss of function allele
                Delta2-3 transposase
                loss of function allele
                P-element activity
                amorphic allele - genetic evidence
                Delta2-3 transposase
                loss of function allele
                Delta2-3 transposase
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                P-element activity
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                P-element activity
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                P-element activity
                amorphic allele - genetic evidence
                P-element activity
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                loss of function allele
                amorphic allele - genetic evidence
                Delta2-3 transposase
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                amorphic allele - genetic evidence
                ethyl methanesulfonate
                References (15)