期刊
G3-GENES GENOMES GENETICS
卷 8, 期 10, 页码 3331-3346出版社
OXFORD UNIV PRESS INC
DOI: 10.1534/g3.118.200627
关键词
Drosophila; brain tumor; neurodegeneration; cell proliferation; prolyl4-hydroxylase
资金
- University of Alabama
- NIH [R03NS090190, R01AG033620]
- University of Wisconsin Graduate School
- Steenbock Professorship
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.
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