A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila

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dc.contributor.authorLoewen, Carin
dc.contributor.authorBoekhoff-Falk, Grace
dc.contributor.authorGanetzky, Barry
dc.contributor.authorChtarbanova, Stanislava
dc.contributor.otherUniversity of Wisconsin Madison
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.date.accessioned2023-09-28T22:05:09Z
dc.date.available2023-09-28T22:05:09Z
dc.date.issued2018
dc.description.abstractA screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, brat(cheesehead) (brat(chs)), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult brat(chs) mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationLoewen, C., Boekhoff-Falk, G., Ganetzky, B., & Chtarbanova, S. (2018). A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in AdultDrosophila. In G3 Genes|Genomes|Genetics (Vol. 8, Issue 10, pp. 3331–3346). Oxford University Press (OUP). https://doi.org/10.1534/g3.118.200627
dc.identifier.doi10.1534/g3.118.200627
dc.identifier.orcidhttps://orcid.org/0000-0001-7865-028X
dc.identifier.orcidhttps://orcid.org/0000-0001-5418-7577
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12321
dc.languageEnglish
dc.language.isoen_US
dc.publisherGenetics Society of America
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDrosophila
dc.subjectbrain tumor
dc.subjectneurodegeneration
dc.subjectcell proliferation
dc.subjectprolyl4-hydroxylase
dc.subjectSTEM-CELL DIFFERENTIATION
dc.subjectSELF-RENEWAL
dc.subjectTRANSCRIPTION FACTORS
dc.subjectPROLYL 4-HYDROXYLASE
dc.subjectNEUROBLAST LINEAGES
dc.subjectCENTRAL COMPLEX
dc.subjectMESSENGER-RNA
dc.subjectNHL DOMAIN
dc.subjectPROTEIN
dc.subjectPROMOTES
dc.subjectGenetics & Heredity
dc.titleA Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophilaen_US
dc.typeArticle
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