A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila
dc.contributor.author | Loewen, Carin | |
dc.contributor.author | Boekhoff-Falk, Grace | |
dc.contributor.author | Ganetzky, Barry | |
dc.contributor.author | Chtarbanova, Stanislava | |
dc.contributor.other | University of Wisconsin Madison | |
dc.contributor.other | University of Alabama Tuscaloosa | |
dc.date.accessioned | 2023-09-28T22:05:09Z | |
dc.date.available | 2023-09-28T22:05:09Z | |
dc.date.issued | 2018 | |
dc.description.abstract | A 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.medium | electronic | |
dc.format.mimetype | application/pdf | |
dc.identifier.citation | Loewen, 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.doi | 10.1534/g3.118.200627 | |
dc.identifier.orcid | https://orcid.org/0000-0001-7865-028X | |
dc.identifier.orcid | https://orcid.org/0000-0001-5418-7577 | |
dc.identifier.uri | https://ir.ua.edu/handle/123456789/12321 | |
dc.language | English | |
dc.language.iso | en_US | |
dc.publisher | Genetics Society of America | |
dc.rights.license | Attribution 4.0 International (CC BY 4.0) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Drosophila | |
dc.subject | brain tumor | |
dc.subject | neurodegeneration | |
dc.subject | cell proliferation | |
dc.subject | prolyl4-hydroxylase | |
dc.subject | STEM-CELL DIFFERENTIATION | |
dc.subject | SELF-RENEWAL | |
dc.subject | TRANSCRIPTION FACTORS | |
dc.subject | PROLYL 4-HYDROXYLASE | |
dc.subject | NEUROBLAST LINEAGES | |
dc.subject | CENTRAL COMPLEX | |
dc.subject | MESSENGER-RNA | |
dc.subject | NHL DOMAIN | |
dc.subject | PROTEIN | |
dc.subject | PROMOTES | |
dc.subject | Genetics & Heredity | |
dc.title | A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila | en_US |
dc.type | Article | |
dc.type | text |
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