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General Information
Name
cancer, neural stem cell, L3MBTL-related
FlyBase ID
FBhh0000773
Disease Ontology Term
Parent Disease
OMIM
Overview

The role of neuroblasts in the development of the Drosophila larval/adult brain has served as a model for the role of adult neural stem cells in normal neural development and in tumor formation. 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. Based on this phenotype, a number of genes impacting this process in flies have been identified. This report describes a human disease model using the fly gene l(3)mbt. In human, there are three genes orthologous to Dmel\l(3)mbt, L3MBTL3, L3MBTL4, and L3MBTL1, which encode chromatin-interacting transcriptional repressors. Loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\l(3)mbt.

None of the three human genes, L3MBTL3, L3MBTL4 or L3MBTL1, has been introduced into flies.

At restrictive temperatures, a temperature-sensitive allele of Dmel\l(3)mbt is lethal in the early pupal stage; the length of the larval stage is greatly extended. The brain hemispheres are up to five times larger in older homozygous larvae raised at the restrictive temperature compared to mature wild-type larvae. Using a tissue transplant assay for neoplastic capacity, homozygous larval brain tissue transplanted into the abdomens of wild-type adult hosts develops into extensive tumors, taking over the entire abdomen of the host in many cases. Physical and genetic interactions have been described for Dmel\l(3)mbt; see below and in the l(3)mbt gene report.

See also related human disease model reports for malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403, FBhh0000404, FBhh0000668).

[updated Mar. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, neural stem cell, L3MBTL-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Neural stem cells have the ability to self-renew and give rise to neurons and glial cells. In Drosophila, the role and regulation of neural stem cells (neuroblasts) at multiple stages has been studied extensively. The study of neuroblasts in the development of the larval/adult brain has served as a model for the role of adult stem cells in normal neural development and in tumor formation.

Genetics
Cellular phenotype and pathology
Molecular information

L3MBTL3, L3MBTL4 and L3MBTL1 encode members of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. [Gene Cards, L3MBTL3; 2018.03.22]

External links
Disease synonyms
malignant glioma, L3MBTL-related
cancer, neuroblast-derived, L3MBTL-related
brain cancer, L3MBTL-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      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 (11 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        molecular sieving, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, ion exchange chromatography
        anti tag coimmunoprecipitation, western blot
        coimmunoprecipitation, western blot
        pull down, western blot
        affinity technology, peptide massfingerprinting, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, molecular sieving, ion exchange chromatography, experimental knowledge based, pull down, autoradiography
        pull down, autoradiography
        tandem affinity purification, Identification by mass spectrometry
        pull down, autoradiography
        Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
        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
        ethyl methanesulfonate
        References (17)