FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: cancer, neural stem cell dedifferentiation
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General Information
Name
cancer, neural stem cell dedifferentiation
FlyBase ID
FBhh0001139
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes use of Drosophila neural stem cells to investigate the processes that normally prevent dedifferentiation. Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state. This process may be implicated in the development of cancer in general and has been proposed, specifically, to contribute to development of glioblastoma.

Notch (N) signaling is central to the self-renewal of neural stem cells (and stem cells of other tissues); Notch hyperactivation in neural stem cells results in dedifferentiation. A number of genes that play a role in this process have been identified, including eukaryotic translation initiation factor 4E (eIF4E1), the transcription factor lola, and the microRNA mir-ban. See also the human disease model report 'cancer, multiple, Notch signaling pathway' (FBhh0000766).

The zinc finger transcription factor nerfin-1 has been characterized extensively in the context of this cancer model. nerfin-1 is expressed in post-mitotic larval neurons and is necessary to maintain their differentiated status. There are two genes orthologous to nerfin-1 in human, the transcriptional regulators INSM1 and INSM2; INSM1 is known to play a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and fetal development. There is a second related gene in Drosophila, nerfin-2. Neither human gene, INSM1 or INSM2, has been introduced into flies.

In order to assess loss-of-function phenotypes of nerfin-1, somatic clones were generated in the larval CNS. In the absence of nerfin-1, neurons dedifferentiate, rapidly increase in size, undergo reversion to acquire a neuroblast cell fate, and become highly proliferative. Clones continue to be highly proliferative during adult stages, producing neural tumors and resulting in a reduced lifespan; these tumors were capable of metastasis when transplanted into the abdomen of naive adult hosts, migrating to distant organs such as the eye. Ectopic expression of nerfin-1 promotes premature differentiation and neuroblast loss. The work in this system primarily addresses the dedifferentiation of type I neural stem cells.

In Drosophila, multiple genes have been found to impact dedifferentiation of type II neural stem cells, including components of the integrator complex. Several recently described neurodevelopmental diseases in human are associated with genes of the integrator complex (see FBhh0001140).

[updated Nov. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, neural stem cell dedifferentiation
OMIM report
Human gene(s) implicated
Symptoms and phenotype

In a mouse model of glioblastoma, it was observed that differentiated cells in the CNS appear to undergo dedifferentiation to generate a neural stem cell or progenitor state to initiate and maintain the tumor progression (Friedmann-Morvinski et al., 2012; pubmed:23087000).

Genetics
Cellular phenotype and pathology
Molecular information

INSM1 encodes a sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. [Gene Cards, INSM1; 2019.11.07]

Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (5)
      Gene Snapshot
      eukaryotic translation initiation factor 4E1 (eIF4E1) encodes a component of the eIF4F cap-binding complex that is essential for cap-dependent translation of mRNA. The product of eIF4E1 binds the 7-methyl-guanosine cap structure of mRNA. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human EIF4E and EIF4E1B (multiple related genes in both species). Dmel\eIF4E1 shares 40-42% identity and 51-62% 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
      nervous fingers 1 (nerfin-1) encodes a zinc finger transcription factor that regulates early axon guidance at the embryonic stage and is required for the maintenance of larval neuron differentiation. In the larval medulla cortex, nerfin-1 is expressed in medulla neurons at the early stage and protects them from dedifferentiation via the repression of Notch signaling pathway. [Date last reviewed: 2018-10-11]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate- to high-scoring ortholog of human INSM1 and INSM2 (2 Drosophila to 2 human). Dmel\nerfin-1 shares 27% identity and 36-37% 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 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
      Gene Snapshot
      longitudinals lacking (lola) encodes a protein involved in Notch signaling, cell death, regulation of retrotransposons and expression of axon and dendrite patterning genes. It contributes to oogenesis, spermatogenesis, neural wiring, eye development and a variety of behaviors. [Date last reviewed: 2019-03-21]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Low-scoring ortholog of human ZBTB20; many related genes in both species.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        5' seed sequence homologous to that of human MIR450B-3p (FBrf0242402).

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (149 groups)
          protein-protein
          Interacting group
          Assay
          References
          anti tag coimmunoprecipitation, anti tag western blot, x-ray crystallography, western blot, isothermal titration calorimetry, predetermined participant, pull down, molecular weight estimation by staining
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry, affinity technology, tag visualisation by luciferase assay
          pull down, western blot, autoradiography
          pull down, western blot
          anti bait coimmunoprecipitation, western blot
          pull down, autoradiography, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, colocalization, fluorescence microscopy, inferred by author, molecular weight estimation by staining, isothermal titration calorimetry, predetermined participant, two hybrid, x-ray crystallography
          anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, enzymatic study, pull down
          anti tag coimmunoprecipitation, peptide massfingerprinting
          pull down, molecular weight estimation by staining
          pull down, molecular weight estimation by staining, anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, anti tag coimmunoprecipitation, two hybrid, affinity chromatography technology, autoradiography, anti tag western blot, Identification by mass spectrometry, classical fluorescence spectroscopy, x-ray crystallography, cosedimentation
          anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot, two hybrid
          anti tag coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
          enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot, fluorescent resonance energy transfer, fluorescence microscopy, anti tag coimmunoprecipitation, two hybrid, pull down, molecular weight estimation by staining, peptide massfingerprinting
          pull down, anti tag western blot, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, two hybrid, far western blotting, autoradiography
          anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot, anti tag coimmunoprecipitation
          pull down, western blot
          pull down, western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, Identification by mass spectrometry, comigration in sds page, anti tag western blot, pull down, covalent binding, western blot
          anti tag coimmunoprecipitation, quantitative reverse transcription pcr, anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry, pull down, molecular weight estimation by staining, anti bait coimmunoprecipitation, anti tag western blot, isothermal titration calorimetry, predetermined participant, peptide massfingerprinting, far western blotting, autoradiography, x-ray crystallography, two hybrid
          anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          RNA-protein
          Interacting group
          Assay
          References
          pull down, western blot
          electrophoretic mobility shift assay, autoradiography
          anti tag coimmunoprecipitation, quantitative reverse transcription pcr, anti bait coimmunoprecipitation, western blot
          RNA-RNA
          Interacting group
          Assay
          References
          luminiscence technology, necessary binding region, immunohistochemistry
          protein-protein
          Interacting group
          Assay
          References
          experimental knowledge based
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          pull down, anti tag western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, western blot
          experimental knowledge based, anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, anti tag western blot
          protein-protein
          Interacting group
          Assay
          References
          two hybrid, enzyme linked immunosorbent assay, electron microscopy, molecular weight
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot, anti tag western blot
          anti bait coimmunoprecipitation, western blot
          proximity ligation assay, fluorescence microscopy
          anti tag coimmunoprecipitation, anti tag 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
          anti tag coimmunoprecipitation, western blot, pull down
          anti tag coimmunoprecipitation, western blot, autoradiography, anti bait coimmunoprecipitation, two hybrid
          proximity ligation assay, fluorescence microscopy
          affinity technology, tag visualisation by alkaline phosphatase activity
          pull down, autoradiography, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation
          affinity technology, inferred by author, bead aggregation assay, fluorescence microscopy, enzyme linked immunosorbent assay, anti bait coimmunoprecipitation, western blot, tag visualisation, phenotype-based detection assay, cross-linking study, pull down, tag visualisation by alkaline phosphatase activity, atomic force microscopy
          pull down, western blot, autoradiography, anti bait coimmunoprecipitation, two hybrid
          anti tag coimmunoprecipitation, western blot, nuclear magnetic resonance, two hybrid, cosedimentation in solution, predetermined participant, anti tag western blot
          anti tag coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
          anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, two hybrid, anti tag western blot
          two hybrid, pull down, western blot, anti tag coimmunoprecipitation
          protease assay, western blot, inferred by author
          anti tag coimmunoprecipitation, anti tag western blot
          three hybrid, protein three hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting
          anti bait coimmunoprecipitation, western blot, two hybrid
          pull down, western blot
          pull down, western blot
          pull down, western blot
          coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot
          pull down, western blot, anti tag coimmunoprecipitation
          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, anti bait coimmunoprecipitation, cross-linking study, western blot, pull down, tag visualisation by alkaline phosphatase activity, affinity technology, fluorescence microscopy, confocal microscopy, bead aggregation assay, tag visualisation, anti tag coimmunoprecipitation
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, pull down
          pull down, molecular weight estimation by staining, isothermal titration calorimetry, predetermined participant, autoradiography, nuclear magnetic resonance, western blot
          protein three hybrid, isothermal titration calorimetry, predetermined participant, two hybrid, pull down, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot, cosedimentation, molecular sieving, molecular weight estimation by staining, anti tag western blot, electrophoretic mobility shift assay, electrophoretic mobility supershift assay, coimmunoprecipitation, electron microscopy, three hybrid
          anti tag coimmunoprecipitation, anti tag western blot
          two hybrid, anti tag coimmunoprecipitation, western blot, pull down
          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
          anti bait coimmunoprecipitation, cross-linking study, western blot
          inferred by author, confocal microscopy, bead aggregation assay
          proximity ligation assay, fluorescence microscopy
          anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry, anti tag western blot
          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
          protein-protein
          Interacting group
          Assay
          References
          pull down, tag visualisation, x ray scattering, two hybrid, molecular sieving, static light scattering, anti bait coimmunoprecipitation, western blot, molecular weight estimation by staining
          anti tag coimmunoprecipitation, western blot, anti tag western blot
          two hybrid, anti tag coimmunoprecipitation, western blot, anti tag western blot
          anti bait coimmunoprecipitation, western blot, pull down, two hybrid
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          two hybrid, two hybrid array, bimolecular fluorescence complementation, fluorescence microscopy
          two hybrid, anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti tag coimmunoprecipitation, anti tag western blot
          RNA-protein
          Interacting group
          Assay
          References
          electrophoretic mobility shift assay, autoradiography, systematic evolution of ligands by exponential enrichment, full identification by DNA sequencing
          anti bait coimmunoprecipitation, full identification by RNA sequencing, anti tag coimmunoprecipitation, quantitative reverse transcription pcr
          RNA-protein
          Interacting group
          Assay
          References
          anti bait coimmunoprecipitation, northern blot, anti tag coimmunoprecipitation, filter binding, competition binding, autoradiography, pull down, western blot, nuclease footprinting
          anti tag coimmunoprecipitation, northern blot, filter binding, autoradiography
          anti tag coimmunoprecipitation, northern blot
          anti tag coimmunoprecipitation, northern blot, electrophoretic mobility shift assay, autoradiography, enzymatic study
          enzymatic study, northern blot
          anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
          anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
          anti tag coimmunoprecipitation, quantitative reverse transcription pcr
          fluorescence polarization spectroscopy, predetermined participant, anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
          enzymatic study, northern blot
          anti tag coimmunoprecipitation, northern blot
          anti tag coimmunoprecipitation, quantitative reverse transcription pcr
          anti tag coimmunoprecipitation, northern blot
          anti tag coimmunoprecipitation, northern blot
          anti tag coimmunoprecipitation, northern blot
          anti tag coimmunoprecipitation, northern blot
          anti bait coimmunoprecipitation, primer specific pcr
          pull down, western blot
          anti tag coimmunoprecipitation, northern blot
          RNA-RNA
          Interacting group
          Assay
          References
          luminiscence technology, necessary binding region
          luminiscence technology, necessary binding region
          luminiscence technology, fluorescence technology, necessary binding region, immunohistochemistry
          luminiscence technology, necessary binding region
          immunohistochemistry, luminiscence technology, necessary binding region
          luminiscence technology, necessary binding region
          western blot, luminiscence technology, necessary binding region, immunohistochemistry
          fluorescence technology
          Alleles Reported to Model Human Disease (Disease Ontology) (40 alleles)
          Models Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 4 )
          Models Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Interaction
          References
          Models Based on Experimental Evidence ( 13 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 22 )
          Allele
          Disease
          Interaction
          References
          is exacerbated by CatHMS00990
          is ameliorated by CatUAS.cUa
          is ameliorated by Sod2UAS.cMa
          is exacerbated by cncHMS00650
          is exacerbated by Sod2HMS00499
          is ameliorated by cncUAS.cSa
          ameliorates  carcinoma
          Models Based on Experimental Evidence ( 1 )
          Modifiers Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Interaction
          References
          Models Based on Experimental Evidence ( 2 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 7 )
          Alleles Representing Disease-Implicated Variants
          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
          Related mammalian, viral, bacterial, or synthetic 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
          Delta2-3 transposase
          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
          ends-in gene targeting
          loss of function allele
          ethyl methanesulfonate
          P-element activity
          P-element activity
          Delta2-3 transposase
          amorphic allele - genetic evidence
          Delta2-3 transposase
          amorphic allele - molecular evidence
          CRISPR/Cas9
          amorphic allele - molecular evidence
          CRISPR/Cas9
          amorphic allele - molecular evidence
          CRISPR/Cas9
          amorphic allele - molecular evidence
          ethyl methanesulfonate
          References (20)